139 results about "Resistant cell" patented technology

The invention provides application of a copper death inducer in preparation of a medicine for treating osimertinib-resistant non-small cell lung cancer, and belongs to the technical field of treatment of non-small cell lung cancer. According to the invention, through high-throughput drug screening, the copper death inducer copper diethyl dithiocarbamate (CuET) and osimertinib are combined for use, so that a remarkable synergistic anti-cancer effect is achieved; furthermore, through detection of a wild type and osimertinib drug-resistant cell line model, an osimertinib sensitive and drug-resistant patient-derived organoid and a mouse xenotransplantation model, it is found that the anti-tumor effect of osimertinib can be remarkably enhanced through copper death induction, and osimertinib drug resistance is overcome. According to the technical scheme provided by the invention, osimertinib drug-resistant non-small cell lung cancer cells can be effectively killed, the curative effect of osimertinib in sensitive and drug-resistant models is remarkably enhanced, and an application scene is provided for copper death in tumor treatment.

This invention discloses a butyrolactone compound with multidrug resistance reverse transcription activity, its preparation method, and its uses. The compound's structural formula is shown in Figure I. The preparation method includes the following steps: fermenting *Aspergillus pyrolyticus* (accession number CCTCC NO: M2014086) to obtain a butyrolactone fermentation product; extracting the fermentation product with ethyl acetate to obtain a crude extract; degreasing the crude extract with hexane and dichloromethane to obtain a final extract; and purifying the final extract using normal-phase silica gel column chromatography, reversed-phase medium-pressure column chromatography, and reversed-phase semi-preparative high-performance liquid chromatography. The advantage of this butyrolactone compound is that it possesses multidrug resistance reverse transcription activity and the ability to regulate P-gp-mediated drug efflux in multidrug-resistant cell lines, making it a potential drug for treating multidrug-resistant cancers.

The invention relates to application of SMARCC1 in preparation of a medicine for treating carfilzomib-resistant multiple myeloma, and belongs to the technical field of biological medicine. According to the invention, direct association between SMARCC1 and the drug resistance of multiple myeloma to carfilzomib is determined for the first time, and the sensitivity of drug-resistant cells to carfilzomib can be significantly enhanced by down-regulating the expression of the gene. Specifically, through systematic analysis on clinical data, SMARCC1 is found to be remarkably and highly expressed in relapse / refractory MM patients and is closely related to poor survival. The SMARCC1 knock-down obviously inhibits the multiplication capacity of multiple myeloma drug-resistant cells, so that the SMARCC1 not only promotes the multiplication capacity of the drug-resistant cells, but also is closely related to the drug resistance of the multiple myeloma cells to carfilzomib, which prompts that the SMARCC1 can be used as a potential therapeutic target and is used for reversing the carfilzomib drug resistance of multiple myeloma.

The application discloses application of Ophisaurus apodus in preparation of a drug for reversing drug resistance of gastric cancer and belongs to the technical field of medicines. The application can reduce tumor volume and size, promote drug resistance cell apoptosis, and reverse the chemotherapeutic drug resistance of a nude mouse with gastric cancer by jointly using Ophisaurus apodus in different parts of the body and cisplatin, by down-regulating P-gp, MRP1 and Bcl-2 protein expression, and by up-regulating Bax protein expression. The effect of the tail + cisplatin group is the most significant.

The invention relates to application of a KRT7-AS inhibitor in preparation of a medicine for treating ovarian cancer or paclitaxel drug resistance of the ovarian cancer. The invention discloses a mechanism of KRT7-AS for promoting ovarian cancer progression by inhibiting ferroptosis for the first time. After KRT7-AS is knocked down by utilizing an shRNA (short hairpin ribonucleic acid) inhibition technology, biological behaviors of ovarian cancer cells and ovarian cancer paclitaxel drug-resistant cells are influenced: proliferation, migration and invasion capabilities are reduced to different degrees, and meanwhile, ferroptosis is activated to inhibit tumor growth. The invention provides a new thought and a potential target for precise treatment of ovarian cancer, and is expected to bring good news to ovarian cancer patients. Long-chain non-coding RNA KRT7-AS is novel carcinogenic lncRNA of ovarian cancer, and the effect of KRT7-AS knockout in the ovarian cancer cell process is researched. By targeting KRT7-AS, ferroptosis of ovarian cancer cells is regulated and controlled, so that tumor progression is influenced. The KRT7-AS inhibitor is used for targeting KRT7-AS, can be used as a treatment method for treating ovarian cancer, and is an innovative strategy for treating ovarian cancer.

This invention relates to drug-resistant breast cancer cells and their applications, belonging to the field of tumor cell technology. The drug-resistant breast cancer cells of this invention are human mammary ductal carcinoma cells T47DR and / or human breast cancer cells MCF7R. The human mammary ductal carcinoma cells T47DR were deposited at the Guangdong Provincial Microbial Culture Collection Center on October 25, 2024, with accession number GDMCC No: 65348; the human breast cancer cells MCF7R were deposited at the same center on October 25, 2024, with accession number GDMCC No: 65347. This invention demonstrates that the clonogenic ability, migration ability, anti-apoptotic ability, and spheroidization ability of drug-resistant breast cancer cells are significantly enhanced. They can form tumors independently of estrogen and metastasize throughout the body in a short period of time. The tumor stemness of the drug-resistant cells is enhanced, and they exhibit resistance to apelexifen and / or tamoxifen.

The invention discloses an application of MetAP2 as a target spot in a drug for reducing drug resistance of multiple myeloma cells. According to the invention, expression of mRNA and protein of MetAP2 in MM drug-resistant cells is increased; when the protein expression of MetAP2 in the MM cells is exogenously changed, the sensitivity of the MM cells to BTZ can be changed; the lifetime of a myeloma mouse model established by using the MM cell for knocking down the MetAP2 is obviously prolonged, and the bone destruction condition is effectively improved. The invention provides a new solution thought for clinically inhibiting tumor growth and improving drug resistance of multiple myeloma, and has important clinical significance and transformation value.

A method for identifying a protein associated with a receptor-ligand interaction is described. The method comprises providing a population of engineered cells comprising a targeting library targeting specific gene expression, contacting the population of cells with a recombinant toxin fusion for sufficient time, and identifying proteins in the selection pool of cells by sequencing one or more of the nucleic acid molecule comprised in the selection pool of cells, thereby identifying the target gene. Toxin-resistant cell lines, toxin-producing cell lines, recombinant toxin fusions, probes and methods producing same, and kits thereof, are also provided.

The invention belongs to the technical field of biological medicine, and particularly relates to application of an anti-HIV drug in inhibition of non-small cell lung cancer drug resistance. The invention finds that the combined use of the anti-HIV drug and EGFR-TKI can effectively and specifically target the MRD drug-resistant cells, inhibit the formation of the MRD drug-resistant cells, significantly improve the curative effect of EGFR-TKI and delay tumor recurrence.

Embodiments disclosed herein use forward genetics tools (e.g., ORF libraries, perturbation libraries) to study fitness advantages under immune pressure, including resistance mechanisms. Once the resistance mechanisms are identified, vulnerabilities (i.e., dependencies) in resistant cells can be identified (e.g., synthetic lethality screens in resistant cancer cells). For example, drug or CRISPR screening can be performed in cells with an identified resistant state. Embodiments disclosed herein also provide targets for resistance to IFN-y treatment.

The invention relates to application of an HOXB9 inhibitor in a medicine for reversing oxaliplatin resistance of gastric cancer, and belongs to the field of biological medicine. The invention discloses for the first time: HOXB9 is remarkably high in expression and is positively correlated with poor prognosis in tissues of patients with gastric cancer, which are poor in curative effect after chemotherapy containing oxaliplatin; by constructing an oxaliplatin drug-resistant gastric cancer cell strain and a patient-derived organ model, the HOXB9 is proved to specifically mediate the survival of the drug-resistant cell strain by activating a focal adhesion signaling pathway (p-FAK / AKT), and the HOXB9 is irrelevant to cell proliferation. Aiming at the mechanism, shRNA nucleic acid molecules (SEQ ID NO: 1-2) targeting HOXB9 are provided, and drug-resistant cell strains can be selectively killed through lentiviral vector delivery, so that the drug-resistant cell IC50 is reduced by more than 50%, the apoptosis rate is increased by 3 times, and the chemotherapy resistance of organoids is reversed. The invention provides a brand-new target spot and a treatment scheme for overcoming the drug resistance of oxaliplatin for gastric cancer.

The invention discloses a 2-amino-4-anilino pyrimidine compound as well as a preparation method and application of the 2-amino-4-anilino pyrimidine compound. The compound has a strong inhibition effect on EGFR (epidermal growth factor receptor) gene mutation targets and c-MET and has a strong inhibition effect on osimertinib drug-resistant cells; and the compound can inhibit proliferation of various tumor cells, and provides excellent application prospects for treatment of EGFR gene mutation and MET amplified malignant tumors.

The invention relates to application of a proteasome inhibitor in preparation of a medicine for treating tumors resistant to a tyrosine kinase inhibitor, and in the application, a plurality of strains of liver cancer cells with drug resistance to lenvatinib or regorafenib are constructed by utilizing a plurality of human liver cancer cell lines with different genetic backgrounds; a high-throughput CRISPR (clustered regularly interspaced short palindromic repeats) gene knockout screening technology and a patent medicine gene CRISPR library are utilized, and gene targets of which the gene knockout or inactivation can better kill drug-resistant cells are specifically identified from thousands of patent medicine genes. Wherein the function inactivation of a plurality of genes in the proteasome family shows more obvious cell killing activity in a plurality of drug-resistant cell models compared with non-drug-resistant cells. The invention discovers and verifies that the proteasome inhibitor has a specific killing effect on tyrosine kinase inhibitor drug-resistant liver cancer for the first time.

The present disclosure relates generally to lipid nanoparticles (LNPs) and compositions comprising the same, and their use for delivering agents, such as nucleic acid-based therapeutic agents, particularly to transfected resistant cells and / or lung tissue.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an HS2ST1 inhibitor in preparation of a medicine for treating KRAS inhibitor drug-resistant tumors. At present, more than 50% of KRAS inhibitor drug-resistant patients have unclear mechanisms and lack of effective intervention targets, and HS2ST1 is identified as a key regulation target of KRAS inhibitor drug resistance for the first time. Researches find that the expression of HS2ST1 in KRAS inhibitor drug-resistant cells is significantly up-regulated; functional experiments prove that targeted intervention of the HS2ST1 can effectively enhance the curative effect of the KRAS inhibitor and reverse the drug resistance phenotype of the KRAS inhibitor, and a new strategy and a potential treatment direction are provided for overcoming KRAS targeted treatment drug resistance.

The application discloses application of AGPG in treatment of endocrine-resistant estrogen receptor positive breast cancer, and finds that AGPG can promote in-vitro endocrine-resistant cell cycle progression and cell proliferation through stable knockout research. Finally, a small interfering RNA drug is tested in an in-vivo experiment, and it is further proved that down-regulation of AGPG mediated by the small interfering RNA can significantly inhibit growth of tamoxifen-resistant MCF7 xenografts.

The application discloses application of cryptoxanthin in preparation of a combination drug for treating lenalidomide-resistant multiple myeloma, and relates to the technical field of medicines.The application verifies the effect and potential mechanism of betaCRY in treating LEN-resistant MM through in-vivo and in-vitro experiments, specifically, betaCRY can inhibit the expression level of FSP1 protein in LEN-resistant tumors, thereby inducing the occurrence of ferroptosis, and then significantly reducing the activity of LEN-resistant tumor cells, and finally achieving the purpose of overcoming LEN tumor drug resistance.The discovery in the application proves that a plant extract serves as a new FSP1 inhibitor in the treatment of LEN-resistant MM cells, and provides a theoretical basis for further using betaCRY to treat LEN-resistant MM in clinic.Therefore, the application has a good application prospect in the field of treating drug-resistant MM.

The invention discloses an application of PINK1 in regulation and control of ER positive breast cancer tamoxifen drug resistance. The invention relates to application of PINK1 as a biomarker in evaluating the tamoxifen resistance of ER positive breast cancer cells. The drug resistance is evaluated by detecting the expression level of PINK1 in a sample and combining mitochondrial autophagy activity. The expression level of the PINK1 comprises an mRNA level and / or a protein level. According to the invention, the drug resistance formation process is systematically analyzed from the perspective of quality control of an organelle of mitochondrial autophagy, and through public database analysis and experimental verification, the overall up-regulation of the mitochondrial autophagy pathway in drug-resistant cells is clearly revealed, and the drug-resistant phenotype is promoted by maintaining the mitochondrial steady state, thereby opening up a new direction for understanding the drug-resistant mechanism.

The application discloses a butyl tin-cycloiridium phenanthroline complex with an aggregation-induced emission (AIE) property, a preparation method of the complex and anticancer application of the complex. The structural formula of the complex is shown as formula (I), and R is one of hydrogen, a phenyl group, a p-tolyl group, a p-bromophenyl group, a p-fluorophenyl group, a biphenyl group, a triphenylamine group, a carbazole group, a tetraphenyl ethene group and a triphenylbenzene group. The growth inhibition rates of the target compound on human alveolar basal epithelial carcinoma cells (A549) and cisplatin-resistant cells (A549 / DDP), cervical cancer cells (Hela) and human lung normal epithelial cells (BEAS-2B) are tested, and it is found through comparison that the target compound shows potential anticancer activity. In addition, the target compound shows unique AIE emission characteristics. The target compound mainly targets the lysosomes of A549 cells, and influences the mitochondria to cause the decline of the mitochondrial membrane potential, thereby showing anticancer activity.

The invention discloses a gold (I) complex containing an alkyne ligand, a preparation method of the gold (I) complex and application of the gold (I) complex in preparation of antitumor drugs, the gold (I) complex has a structure as shown in a general formula I, a phosphorus ligand is selected from diphenyl-2-pyridine phosphine or tricyclohexylphosphine, and Rx is an organic group selected from a specific alkyne ligand; according to the preparation method, chloroauric acid is taken as an initial raw material, sequentially reacts with dimethyl sulfide and an organic phosphine ligand, and finally is coupled with an alkyne ligand under an alkaline condition, so that the steps are simple and convenient, the conditions are mild, and the yield is high; in-vitro activity experiments show that the complex shows remarkable proliferation inhibition activity on ovarian cancer, malignant melanoma, non-small cell lung cancer and cisplatin-resistant cell strains thereof, the effect of the complex is superior to that of cisplatin and auronafine, and a candidate compound is provided for developing a novel targeted anti-tumor drug for overcoming the drug resistance of platinum drugs.

The invention discloses an alpha2delta1 targeted degradation molecule alpha2delta1-LYTAC as well as a derivative and application thereof. The alpha2delta1 targeted degradation molecule alpha2delta1-LYTAC comprises an alpha2delta1 antagonistic polypeptide with an amino acid sequence as shown in SEQ ID No: 1 and a medicine. The alpha2delta1-LYTAC can be combined with alpha2delta1, the alpha2delta1 protein is degraded by combining with the alpha2delta1, and a downstream signal channel of the alpha2delta1 protein is blocked, so that liver cancer cell proliferation is inhibited, liver cancer cell apoptosis is promoted, especially tumor drug-resistant cells are promoted, effective small molecule drugs for treating liver cancer and the like are provided, and the alpha2delta1-LYTAC can be widely applied to the fields of medicine and biology.

The present disclosure relates to eukaryotic cell lines with a stable integrated loss-of-function or attenuation-of-function mutation in each of the Bax and Bak genes. Also provided are methods of producing such cell lines. This disclosure also relates to compositions and cell cultures comprising such cell lines, as well as methods of producing a product, such as a recombinant polypeptide or viral vector, using said cells, compositions and cell cultures.

The invention relates to the technical field of biomedicine, in particular to a third-generation ALK TKI drug loratinib drug-resistant cell strain as well as a construction method and application thereof, the drug-resistant cell strain is a loratinib-resistant human non-small cell lung cancer cell strain H3122 LS and is preserved in Guangdong Microbial Culture Collection Center on July 25, 2025, and the preservation number is GDMCC No: 66760. According to the invention, an EML4-ALK fusion driven H3122 cell is treated by using a third generation of ALK TKI loratinib, a cell with high drug resistance to loratinib is formed through induction, and it is found that the drug-resistant cell loses EML4-ALK fusion variation. At present, the drug-resistant mechanism of the ALK inhibitor is not clarified clinically, and the construction of the drug-resistant cell and the discovery of the drug-resistant mechanism are beneficial to guiding clinical discovery of a new potential drug-resistant mechanism; a new drug-resistant related driver gene or signal pathway is found, and an experimental basis is provided for subsequent treatment strategy selection of a drug-resistant patient.

The invention discloses an aminopeptidase N nano-antibody, a preparation method thereof and application of the aminopeptidase N nano-antibody in overcoming gastric cancer chemotherapy drug resistance, and belongs to the technical field of nano-antibodies. And the amino acid sequence of the heavy chain variable region of the aminopeptidase N nano antibody is as shown in SEQ ID NO.6. The invention discloses a neutralizing type nano antibody for specifically targeting aminopeptidase N (APN). Firstly, it is verified in vitro that the antibody has high affinity and neutralizing activity on APN protein, and it is verified that in a gastric cancer chemotherapy drug-resistant cell line, when the antibody is combined with a gastric cancer chemotherapy drug, cell drug resistance can be synergistically blocked; subsequently, a gastric cancer in-situ drug-resistant transplantation tumor model on an animal living body level further proves that the antibody can effectively inhibit APN in an animal body in a targeted manner, and the chemotherapy curative effect is remarkably enhanced under the condition of drug combination. In conclusion, the APN neutralizing nano antibody prepared by the invention provides a new solution for overcoming the chemotherapy drug resistance of gastric cancer and improving the prognosis of patients.

The application discloses application of a Blautia in preparation of a drug for enhancing sensitivity of colorectal cancer to oxaliplatin, B-CM can significantly enhance OXa cytotoxicity on drug-resistant colorectal cancer cells, inhibit proliferation, clone formation, migration and invasion ability. Combination therapy can synergistically induce apoptosis, although the expression of MDR1 in drug-resistant cells is up-regulated, but the combination of B-CM and OXa can significantly reduce the mRNA and protein levels. In vivo experiments show that B-CM enhances the tumor inhibition effect of OXa, which is related to the reduction of the expression of Ki-67 and MDR1 in tumor tissues. Further, it can be shown that the soluble factor derived from Blautia can reverse the drug resistance of colorectal cancer to oxaliplatin by down-regulating MDR1 and inhibiting epithelial-mesenchymal transition. This shows that Blautia-derived metabolites are a promising new adjuvant strategy to overcome chemotherapy resistance of colorectal cancer.

Bispecific antibody against EGFR and c-Met. The heterodimeric interaction between the EGFR binding arm and the c-Met binding arm of the bispecific antibody is stronger than the interaction of each in the source homodimer by modifying the Fc segment amino acid sequence of the binding arm, so that it can be assembled into a heterodimer in vitro; its effect on inhibiting the proliferation of EGFR and c-Met double-positive tumor cells is stronger than the combination of EGFR monoclonal antibody and c-Met monoclonal antibody, mediates antibody-dependent cellular cytotoxicity (ADCC), promotes target protein internalization and inhibits the proliferation of osimertinib acquired resistant cell lines. Since the prepared bispecific antibody is simple to prepare, stable in structure, and can obtain a pure bispecific antibody by in vitro assembly, it is expected to better meet the clinical treatment needs, and therefore has a good market prospect.

The invention provides synthesis and application of a tetravalent platinum prodrug with a mitochondrial GLS / mt-DNA dual-targeting function. According to the invention, oxaliplatin-resistant liver cancer cell mitochondria is taken as a target spot, tetravalent platinum is taken as a skeleton template, a double-drug multifunctional tetravalent platinum prodrug (LND-Pt-TPP) capable of co-targeting mitochondria GLS1 and mt-DNA is synthesized, and liver cancer treatment sensitivity of oxaliplatin is restored by intervening drug-resistant cell glutamine metabolism and avoiding DNA damage repair. The pharmaceutical composition is used for treating oxaliplatin-resistant liver cancer. The invention further studies the action mechanism that the tetravalent platinum prodrug (LND-Pt-TPP) with the mitochondrial GLS / mt-DNA dual-targeting function intervenes in GLS1 mediated glutamine metabolism to increase the formation of an mt-DNA-Pt compound, and has very important clinical application value.

The invention discloses application of an AKT inhibitor or an STAT3 inhibitor in preparation of a medicine for overcoming drug resistance of bladder cancer to an MEK inhibitor, and belongs to the field of biological medicine. Detecting the cell activity through an MTT method; a Western blot experiment is adopted to detect a key target protein or gene expression level, a bladder cancer drug-resistant cell ERK abnormal activation + STAT3 / Akt compensation activation mechanism is defined, p-ERK, p-STAT3 and p-Akt are locked as targets, the drug resistance of bladder cancer to an MEK inhibitor is overcome through an AKT inhibitor or an STAT3 inhibitor, the scheme can accurately inhibit abnormal pathways, reverse drug resistance and improve treatment sensitivity, and the method is safe and suitable for clinical application. A new direction is provided for patients with drug-resistant bladder cancer, and the clinical bottleneck of the MEK inhibitor is helped to be broken through.

The application discloses application of lumacaftor in improving paclitaxel resistance of triple-negative breast cancer, and belongs to the technical field of biological medicine. The application provides application of a drug composition in preparation of a drug for preventing and / or treating paclitaxel-resistant triple-negative breast cancer; and an active ingredient of the drug composition is lumacaftor and paclitaxel. It is found for the first time that lumacaftor can significantly enhance the killing effect of paclitaxel on TNBC drug-resistant cells, and the mechanism may be related to inhibition of glycolysis pathway, recovery of cell cycle arrest and promotion of apoptosis signal. Experimental results prove that, as a GTM1 agonist, lumacaftor can inhibit the AMPK-glycolysis pathway and reduce lactic acid generation; in combination with paclitaxel in paclitaxel-resistant cells, cell proliferation is significantly inhibited, but the effect is not significant in parent cells. Therefore, lumacaftor can be used as a chemosensitizer for paclitaxel-resistant triple-negative breast cancer, and has a clear mechanism and good application prospect.

The invention relates to the technical field of biology, and particularly discloses a construction method and application of an ADC target drug-resistant strain, human gastric cancer cell strain NCI-N87 cells are treated by DS-8201 with different concentrations, a gastric cancer DS-8201 drug-resistant cell line is established by adopting a method of gradually increasing the drug concentration, and the concentration is taken as a screening concentration to continuously stimulate the cells for a long time, so that the drug-resistant cell line is obtained. And finally, the gastric cancer DS-8201 drug-resistant cell strain (NCI-N87 / DS-8201 R) is obtained. The DS-8201 tolerance concentration of the NCI-N87 / DS-8201 R reaches 200 ng / mL or above, and the NCI-N87 / DS-8201 R has high drug resistance. The cell strain can be used for in-vivo and in-vitro experiments of a gastric cancer tumor DS-8201 drug resistance mechanism, evaluation of antitumor activity of drugs and assistance in screening of target drugs for reversing drug resistance.