Application of honokiol in preparation of medicine for treating retinoblastoma

Abstract

The invention relates to the technical field of medicine application, discloses application of honokiol in preparation of a medicine for treating retinoblastoma, and finds that honokiol has a new effect of treating retinoblastoma for the first time, can effectively inhibit proliferation of retinoblastoma cells, and has a good application prospect in treatment of retinoblastoma. And the application has important significance for developing a novel medicine for treating the retinoblastoma. Experiments prove that honokiol can inhibit proliferation of RB cells by promoting RB cell apoptosis and inducing cell cycle arrest. The application also finds that honokiol has a remarkable treatment effect on multidrug-resistant RB cells for the first time, and a new thought is provided for solving the clinical problem of RB chemotherapy drug resistance. Tests prove that honokiol still keeps good sensitivity to RB drug-resistant cells, and the killing effect of honokiol on RB / CBP drug-resistant cells is similar to that of RB non-drug-resistant cells.

Description

Technical Field

[0001] The present application relates to the technical field of drug application, and in particular to an application of honokiol in the preparation of a drug for treating retinoblastoma. Background Art

[0002] Retinoblastoma (RB) is a dangerous intraocular malignancy that usually occurs before the age of 5. There are approximately 9,000 new cases worldwide each year, ranking first among intraocular malignancies. RB is the leading cause of blindness in children and is prone to intracranial and distant metastasis, often endangering children's lives.

[0003] Early treatment of RB is mostly local radiotherapy, photocoagulation or cryotherapy. For patients with advanced RB, chemotherapy-based combined treatment is often used. However, chemotherapy is prone to drug resistance and inevitable toxicity. Among them, multidrug resistance is the main obstacle to clinical treatment and an important cause of chemotherapy failure. Therefore, it is urgent to develop new RB treatment drugs that are safe, effective and resistant to chemotherapy resistance.

[0004] Natural products have been considered an important source of clinical drugs, and many widely used effective ingredients of traditional Chinese medicine have a good killing effect on tumors. Honokiol (HNK) is a bisphenol plant compound extracted from the bark and cones of the traditional Chinese medicine Magnolia officinalis, which has multiple pharmacological effects such as anti-cancer, anti-inflammatory, antibacterial, and antioxidant. At present, the therapeutic effect of HNK on RB, especially the anti-RB effect, has not been reported. Summary of the invention

[0005] In view of this, the present application provides an application of magnolol in the preparation of a drug for treating retinoblastoma, so as to solve the problem of poor treatment effect of retinoblastoma, especially the problem of chemotherapy failure caused by multidrug resistance generated during RB cell treatment.

[0006] In a first aspect, the present application provides a use of magnolol in the preparation of a drug for treating retinoblastoma.

[0007] In an optional embodiment, the structural formula of honokiol in the use of honokiol in the preparation of a drug for treating retinoblastoma is as follows:

[0008]

[0009] In an optional embodiment, the drug is a drug that has an inhibitory effect on human retinal glioma cells.

[0010] In an optional embodiment, the drug has the effect of inducing apoptosis of human retinal glioma cells.

[0011] In an optional embodiment, the drug has the effect of upregulating the expression of caspase-3 in human retinal glioma cells.

[0012] In an optional embodiment, the drug has the effect of down-regulating the expression of survivin in human retinal glioma cells.

[0013] In an optional embodiment, the drug has the effect of inducing cell cycle arrest of human retinal glioma cells.

[0014] In an optional embodiment, the drug has an inhibitory effect on drug-resistant human retinal glioma cells.

[0015] In an optional embodiment, the drug has an inhibitory effect on carboplatin (CBP)-resistant human retinal glioma cells.

[0016] Compared with the prior art, the beneficial effects of this application are:

[0017] The present application provides an application of honokiol in the preparation of a drug for treating retinoblastoma. It is the first time that honokiol has a new effect in treating retinoblastoma and can effectively inhibit the proliferation of retinoblastoma cells, which is of great significance for the development of new drugs for treating retinoblastoma. Experiments have shown that honokiol can inhibit the proliferation of RB cells by promoting RB cell apoptosis and inducing cell cycle arrest.

[0018] This application also found for the first time that honokiol has a significant therapeutic effect on multidrug-resistant RB cells, providing a new idea for solving the clinical problem of RB chemotherapy resistance. Experiments have shown that honokiol still maintains good sensitivity to RB resistant cells, and its killing effect on RB / CBP resistant cells is similar to that of RB non-resistant cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0020] Figure 1 The CCK-8 method in Experimental Example 1 of the present application detects the inhibitory effect of HNK on RB cells;

[0021] Figure 2a The apoptosis of RB cells induced by HNK was detected by flow cytometry in Experimental Example 1 of the present application;

[0022] Figure 2b It is a comparison of the apoptosis rate of RB cells induced by different concentrations of HNK solution in Experimental Example 1 of the present application;

[0023] Figure 3 The effect of HNK on RB cell apoptosis was detected by cell immunofluorescence in Experimental Example 1 of the present application;

[0024] Figure 4a The flow cytometry method for detecting HNK-induced RB cell cycle arrest in Experimental Example 1 of the present application;

[0025] Figure 4b It is a comparison of the RB cell cycle arrest induced by different concentrations of HNK solution in Experimental Example 1 of the present application;

[0026] Figure 5 The RB cells and RB / CBP-resistant cells were observed under a microscope in Experimental Example 2 of the present application;

[0027] Figure 6 is the growth curve of RB cells and RB / CBP-resistant cells in Experimental Example 2 of the present application;

[0028] Figure 7 The inhibitory effects of carboplatin, etoposide, and vincristine on RB cells and RB / CBP-resistant cells in Experimental Example 2 of the present application;

[0029] Figure 8 This is the inhibitory effect of magnolol at different concentrations and at different time points on RB / CBP-resistant cells in Experimental Example 2 of the present application. DETAILED DESCRIPTION

[0030] The following examples are provided for a better understanding of the present application, but are not limited to the best implementation mode described, and do not limit the content and protection scope of the present application. Any product identical or similar to the present application obtained by anyone under the inspiration of the present application or by combining the features of the present application with other prior arts shall fall within the protection scope of the present application.

[0031] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0032] In the present application, the percentage content, unless otherwise specified, refers to mass percentage for solid-liquid mixing and solid-solid mixing, and refers to volume percentage for liquid-liquid mixing.

[0033] In this application, when it comes to percentage concentration, unless otherwise specified, it refers to the final concentration. The final concentration refers to the proportion of the added component in the system after the addition of the component.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0035] The present application does not specifically limit the method for obtaining honokiol, and it can be prepared by conventional methods in the art, which is implemented by those skilled in the art, or it can be purchased from the market. The honokiol used in the following experiments is a conventionally purchased honokiol standard.

[0036] The chemical structural formula of Honokiol (HNK) is:

[0037]

[0038] The human retinal glioma cells WERI-Rb-1 (RB cells) used in the following experiments were purchased from the cell bank of the Chinese Academy of Sciences and cultured in RPMI-1640 cell culture medium containing 10% fetal bovine serum and 100 U / ml penicillin / streptomycin in a 37°C, 5% CO2 incubator.

[0039] RPMI-1640 cell culture medium was purchased from Gibco, USA;

[0040] DMSO was purchased from Gibco, USA;

[0041] Honokiol was purchased from Beijing Solaibao Technology Co., Ltd., China;

[0042] Carboplatin was purchased from Beijing Solebao Technology Co., Ltd., China;

[0043] Etoposide was purchased from Beijing Solebao Technology Co., Ltd., China;

[0044] Vincristine was purchased from Beijing Solebow Technology Co., Ltd., China.

[0045] The present application is further described in detail below in conjunction with specific examples, and these examples should not be construed as limiting the scope of protection claimed in the present application. If no specific experimental steps or conditions are specified in the following experiments, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional reagent products that can be obtained commercially.

[0046] Experimental Example 1: Inhibitory Effect of HNK on RB Cells

[0047] 1. CCK-8 assay to determine the inhibitory effect of HNK on RB cells

[0048] RB cells were treated with HNK at different concentrations (0, 20μM, 40μM, 60μM, 80μM, 100μM, 120μM) to study the inhibitory effect of HNK on RB cell proliferation, and CCK-8 was used to detect the survival rate of RB cells at different time points (24h and 48h). The details are as follows:

[0049] RB cells in the logarithmic growth phase were seeded in 96-well plates, with 5×10 3 cells. HNK was prepared into a 1mM stock solution using DMSO, and then diluted into HNK solutions of different concentrations using serum-free cell culture medium (RPMI-1640 cell culture medium). Experimental groups 1-6 were added with equal volumes of HNK solutions with final concentrations of 20μM, 40μM, 60μM, 80μM, 100μM or 120μM, respectively, and the control group was added with an equal volume of DMSO solvent control. Each group was cultured for 24h and 48h, respectively. Then, 20μl of CCK-8 reagent was added to each well and cultured for 3h. The absorbance value (OD) was measured at 450nm using an enzyme reader. The experimental results are shown in the figure. Figure 1 , where the horizontal axis is the concentration of HNK solution, and the vertical axis is the survival rate of RB cells; the left figure shows the inhibitory effect of HNK on RB cell proliferation when RB cells are cultured for 24 hours; the right figure shows the inhibitory effect of HNK on RB cell proliferation when RB cells are cultured for 48 hours.

[0050] The results showed that compared with the control group, the addition of HNK solution at concentrations of 40μM, 60μM, 80μM, 100μM and 120μM could significantly inhibit the proliferation of RB cells, and with the increase of HNK concentration and the extension of inhibition time, the survival rate of RB cells continued to decrease (P<0.001), that is, the inhibitory effect of HNK was dose- and time-dependent.

[0051] 2. Honokiol inhibits RB cell proliferation by inducing apoptosis

[0052] Annexin V-FITC / PI double staining was used to detect cell apoptosis rate. RB cells in the logarithmic growth phase were inoculated in 6-well plates, with 1×10 6 cells. HNK was prepared into a 1mM stock solution using DMSO, and then diluted into HNK solutions of different concentrations using serum-free cell culture medium (RPMI-1640 cell culture medium). The experimental groups were added with equal volumes of HNK solutions with final concentrations of 40μM and 60μM, respectively, and the control group was added with equal volumes of DMSO solvent control, and cultured for 24h. The cells were collected by centrifugation, washed twice with ice-cold PBS, and resuspended. FITC-labeled Annexin-V and propidium iodide (PI) solution were added and cultured for 15 minutes at room temperature in the dark. The cell apoptosis rate was detected by flow cytometry.

[0053] In addition, cell immunofluorescence was used to detect HNK-induced RB cell apoptosis. RB cells in the logarithmic growth phase were inoculated in 6-well plates, with 1×10 6 cells. The experimental groups were added with equal volumes of HNK solutions with final concentrations of 40 μM and 60 μM, respectively, and the control group was added with equal volumes of DMSO solvent control, and cultured for 24 hours. The cells were collected by centrifugation, washed with PBS, and fixed with 4% paraformaldehyde. The cells were permeabilized with Triton X-100 (0.5%) and blocked with 5% BSA. Then, the cells were cultured with caspase-3 or survivin primary antibodies at 1:500 at 4°C overnight. The cells were washed 3 times with TBST and cultured with fluorescently conjugated secondary antibodies. After washing 3 times with PBST, DAPI staining was performed for 1 minute.

[0054] Flow cytometry was used to detect the apoptosis of RB cells induced by HNK. Figure 2a As shown in Figure 2, the apoptosis rate of RB cells induced by different concentrations of HNK solution was compared as shown in Figure 2. Figure 2b , where the horizontal axis represents cell apoptosis at different stages, and the vertical axis represents cell apoptosis rate.

[0055] As can be seen from the figure, the apoptosis rate of RB cells in the HNK (40μM and 60μM) treatment group was significantly increased, and the apoptosis rate of RB cells in the HNK high-dose group was significantly higher than that in the HNK low-dose group. The results showed that after 24h, compared with the control group (early and late apoptotic cell rates were 11.20% and 9.64%, respectively), HNK 60μM (early and late apoptotic cell rates were 15.72% and 51.83%, respectively) stimulation significantly increased the proportion of early and late apoptotic cells in RB cells (P<0.01), and HNK mainly increased the late apoptosis of RB cells. The above results show that HNK can inhibit RB cell proliferation by inducing apoptosis.

[0056] The results of cell immunofluorescence analysis showed that Figure 3 Compared with the control group, HNK (40μM and 60μM) stimulation can upregulate the expression of caspase-3 and downregulate the expression of survivin in RB cells, and the effect of the high-dose HNK group is more significant. The above results show that HNK induces apoptosis by changing the expression of caspase-3 and survivin in RB cells.

[0057] 3. Honokiol inhibits RB cell proliferation by inducing cell cycle arrest

[0058] Flow cytometry was used to detect HNK-induced RB cell cycle arrest. RB cells in the logarithmic growth phase were seeded in 6-well plates, with 1×10 6cells. The experimental groups were added with equal volumes of HNK solutions with final concentrations of 40μM and 60μM, respectively, and the control group was added with equal volumes of DMSO solvent control, and cultured for 24h. The cells were collected by centrifugation, fixed with 70% ethanol precooled to 4°C overnight, and then stained with 400μl of PI solution and 100μl of ribonuclease A solution. The concentration of PI solution was 50μg / ml and the concentration of ribonuclease A (Ribonuclease A, RNase A) solution was 100μg / ml at room temperature in the dark for 15min. Then the RB cell cycle distribution was detected by flow cytometry.

[0059] Flow cytometry was used to determine whether HNK inhibits RB cell proliferation by inducing cell cycle arrest. To evaluate the effect of HNK on RB cell cycle, we treated RB cells with different concentrations of HNK solution (0, 40 μM, 60 μM) for 24 h. The results of the flow cytometry assay to detect HNK-induced RB cell cycle arrest are shown in Figure 2. Figure 4a As shown, the comparison of RB cell cycle arrest induced by different concentrations of HNK solution is shown in Figure 4b As shown, the horizontal axis represents cells in different groups, and the vertical axis represents the cell cycle ratio.

[0060] Different concentrations of HNK solution (40μM and 60μM) can significantly increase the proportion of RB cells in the G0 / G1 phase (p<0.05; p<0.01). The above results show that HNK can inhibit the proliferation of RB cells by inducing RB cell cycle arrest in G0 / G1.

[0061] Experimental Example 2 Inhibitory Effect of Honokiol on Carboplatin-Resistant Retinoblastoma Cells

[0062] 1. Construction of RB / CBP-resistant cells

[0063] The RB / CBP-resistant cells (RB cells stably grown in carboplatin solution) were constructed by stimulation with increasing carboplatin concentrations, as follows: RB cells in the logarithmic growth phase were seeded in a 96-well plate, with 5×10 3The cells were stimulated for the first time with a low concentration of 25μM carboplatin solution (carboplatin solution configuration: CBP was prepared into a 10mM stock solution with serum-free medium, and then diluted into carboplatin solutions of different concentrations with serum-free cell culture medium, and the serum-free cell culture medium was RPMI-1640 cell culture medium). The cells were stimulated for 2h, then centrifuged, and washed once with 5ml serum-free cell culture medium. After centrifugation, fresh cell culture medium (RPMI-1640 cell culture medium containing 10% fetal bovine serum and 100U / ml penicillin / streptomycin) was added for culture. Some cells died until the living cells grew to a certain concentration again (i.e., a large number of cell clusters appeared). The above steps were repeated again and the same concentration and volume of carboplatin solution were used for stimulation. This concentration of carboplatin solution was used for a total of 3-4 times. After the RB cells can grow stably in the 25μM carboplatin solution (i.e., a large number of cell clusters can appear), the same volume of carboplatin solution with a higher concentration was added. The stimulation was performed by increasing the concentration of carboplatin solution by 25 μM each time (the stimulation concentrations of carboplatin solution were 50 μM, 75 μM, 100 μM, 125 μM, and 150 μM, respectively). The stimulation process was the same as above. After the RB cells could grow stably in the carboplatin solution with increasing concentration, the concentration of the carboplatin solution was increased.

[0064] The experimental results showed that after 6 months of intermittent stimulation with increasing carboplatin concentration, RB / CBP-resistant cells were able to grow stably in a carboplatin solution with a final concentration of 150 μM. RB cells without carboplatin stimulation and RB / CBP-resistant cells stimulated with carboplatin solution (RB cells growing stably in a carboplatin solution with a final concentration of 150 μM) were observed under a microscope. Figure 5 As shown. Comparative observation of RB cells and RB / CBP-resistant cells under a microscope revealed that RB cells had a high growth density and were prone to clustering in the shape of grapes, while RB / CBP-resistant cells had a low growth density and were more dispersed and less likely to cluster. In summary, RB / CBP-resistant cells were constructed through stimulation with increasing carboplatin concentrations and are awaiting further drug sensitivity testing.

[0065] 2. Growth of RB / CBP-resistant cells

[0066] RB cells and RB / CBP-resistant cells in logarithmic growth phase were seeded in 96-well plates, with 5×10 3 Each well was cultured for 0, 12, 24, 48, 72, and 96 hours. Then, 20 μl of CCK-8 reagent was added to each well and cultured for 3 hours. The absorbance (OD) was measured at 450 nm using a microplate reader. The growth curves of RB cells and RB / CBP-resistant cells were plotted with the absorbance as the vertical axis and the time as the horizontal axis, and then the growth curves before and after drug resistance were compared.

[0067] Growth curves of RB cells and RB / CBP-resistant cells are shown in Figure 2 Figure 6 As shown in the figure; the left figure is the growth curve of RB cells; the right figure is the growth curve of RB / CBP-resistant cells; as shown in the figure, starting from 12h, as the culture time increases, the proliferation of the two groups of cells gradually increases, but the proliferation of RB / CBP-resistant cells is significantly lower than that of RB cells. Compared with RB cells, RB / CBP-resistant cells grow more slowly, the highest cell concentration is lower, and the time for cell concentration to reach the peak is delayed (RB cell concentration peak time is 48h, RB / CBP-resistant cell concentration peak time is 72h). The above results show that the proliferation of carboplatin-resistant RB cells is reduced, and the main pathway of their recurrence or metastasis may not occur through cell proliferation.

[0068] 3. Determination of drug sensitivity and multidrug resistance of CBP / RB resistant cells

[0069] CCK-8 method was used to detect the sensitivity of RB cells and RB / CBP-resistant cells to carboplatin, etoposide and vincristine. The details are as follows:

[0070] RB cells in the logarithmic growth phase were inoculated into 96-well plates, with 5 × 10 3 The same volume of carboplatin solution containing concentration gradient (50 μM, 100 μM, 200 μM, 300 μM, 400 μM) was added to each well of cells, and the absorbance value (OD) of each well was measured after culturing for 24 hours.

[0071] Take RB / CBP-resistant cells in the logarithmic period and add 5×10 3 The same volume of carboplatin solution containing concentration gradient (100 μM, 200 μM, 400 μM, 800 μM, 1000 μM) was added to each well of cells, and after culturing for 24 h, the absorbance value (OD) of each well was measured.

[0072] Tumor cell survival rate (%) = absorbance of experimental well (OD) / absorbance of control well (OD) × 100%, calculate the half inhibitory concentration (IC50); RB / CBP-resistant cells to carboplatin resistance index (RI) = IC50 (RB / CBP-resistant cells) / IC50 (RB cells).

[0073] According to the above steps, etoposide (VP) or vincristine (VCR) was used to prepare etoposide solution or vincristine solution with gradient concentration, and added to equal amount of RB cells or RB / CBP resistant cells in logarithmic growth phase, respectively, and cultured for 24 hours, and then the absorbance value (OD) of each well was measured. The IC50 and resistance index RI of etoposide and vincristine on RB cells and CBP / RB resistant cells were calculated.

[0074] Inhibitory effects of carboplatin, etoposide, and vincristine on RB cells and RB / CBP-resistant cells Figure 7 As shown, the horizontal axis is the concentration of the drug solution, and the vertical axis is the survival rate of tumor cells; a is the inhibitory effect of carboplatin on RB cells; b is the inhibitory effect of carboplatin on RB / CBP-resistant cells; c is the inhibitory effect of etoposide on RB cells; d is the inhibitory effect of etoposide on RB / CBP-resistant cells; e is the inhibitory effect of vincristine on RB cells; f is the inhibitory effect of vincristine on RB / CBP-resistant cells.

[0075] The resistance of RB / CBP-resistant cells to carboplatin, etoposide and vincristine is shown in Table 1 .

[0076] Table 1 Comparison of drug resistance between RB cells and RB / CBP-resistant cells

[0077]

[0078] According to the drug resistance judgment standard (resistance index RI <5 is low resistance, 5-15 is moderate resistance, >15 is high resistance), it can be seen that RB / CBP resistant cells are moderately resistant to etoposide and vincristine, and lowly resistant to CBP. It can be concluded that after 6 months of intermittent stimulation of RB cells with gradient concentrations of carboplatin, RB / CBP resistant cells showed significant multidrug resistance.

[0079] 4. Inhibitory effect of honokiol on RB / CBP-resistant cells

[0080] The CCK-8 method was used to determine the inhibitory effect of HNK on RB / CBP-resistant cells.

[0081] RB / CBP-resistant cells in the logarithmic growth phase were seeded in 96-well plates, with 5×10 3 The experimental groups were added with equal volumes of HNK solutions with final concentrations of 30 μM, 40 μM and 50 μM, respectively, and the control group was added with equal volumes of DMSO solvent control. The cells were cultured for 24 h and 48 h, respectively, and the absorbance value (OD) of each well was measured. The inhibitory effects of different concentrations of HNK on RB / CBP-resistant cells were shown in Figure 2. Figure 8 shown.

[0082] Figure 8 The left figure shows the inhibitory effect of HNK at different concentrations and at different time points on RB / CBP-resistant cells; the right figure shows the inhibitory effect of HNK at different concentrations on RB / CBP-resistant cells at 24 hours of culture; the right figure shows the inhibitory effect of HNK at different concentrations on RB / CBP-resistant cells at 48 hours of culture.

[0083] As can be seen from the figure, with the increase of HNK concentration, the inhibition rate of RB / CBP-resistant cells increased significantly. The results showed that different concentrations of HNK (30μM, 40μM, 50μM) could inhibit the proliferation of RB / CBP-resistant cells to varying degrees (P < 0.001), and the inhibitory effect increased with the increase of HNK concentration and the extension of culture time. It can be seen that HNK still maintains a good sensitivity to RB / CBP-resistant cells, and the inhibitory intensity of RB / CBP-resistant cells is similar to that of RB non-resistant cells.

[0084] In summary, this application first discovered the new effect of honokiol in treating RB, which can effectively inhibit the proliferation of RB cells, and is of great significance for the development of new therapeutic drugs for RB. As can be seen from Experimental Example 1, honokiol can significantly inhibit the proliferation of RB cells, and with the increase of honokiol drug concentration and the extension of inhibition time, the survival rate of RB cells continues to decrease, showing dose and time dependence. Honokiol can inhibit the proliferation of RB cells by promoting RB cell apoptosis and inducing cell cycle arrest.

[0085] This study also discovered for the first time that magnolia officinalis has a significant therapeutic effect on multidrug-resistant RB cells, providing a new idea for solving the clinical problem of RB chemotherapy resistance. Chemotherapy is an important treatment for RB, but chemotherapy multidrug resistance is the main obstacle to clinical treatment and an important cause of chemotherapy failure. As can be seen from Experimental Example 2, multidrug-resistant RB cells were successfully constructed after 6 months of stimulation by intermittent stimulation of RB cells with gradient concentrations of carboplatin. Experiments have shown that magnolia officinalis still maintains a good sensitivity to RB resistant cells, and its killing effect on RB / CBP resistant cells is similar to that of RB non-resistant cells.

[0086] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection created by this application.

Claims

1. A use of honokiol in preparing a drug for treating retinoblastoma, characterized in that: The structural formula of the honokiol is as follows:

2. The use according to claim 1, characterized in that: The drug is a drug that has an inhibitory effect on human retinal glioma cells.

3. The use according to claim 2, characterized in that: The drug has the effect of inducing apoptosis of human retinal glioma cells.

4. The use according to claim 3, characterized in that: The drug has the effect of up-regulating the expression of caspase-3 in human retinal glioma cells.

5. The use according to claim 3, characterized in that: The drug has the effect of down-regulating the expression of survivin in human retinal glioma cells.

6. The use according to claim 3, characterized in that: The drug has the effect of inducing cell cycle arrest of human retinal glioma cells.

7. The use according to any one of claims 1 to 6, characterized in that: The drug has an inhibitory effect on drug-resistant human retinal glioma cells.

8. The use according to claim 7, characterized in that: The drug has an inhibitory effect on carboplatin-resistant human retinal glioma cells.

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