Gene medicine for promoting differentiation of tumor stem cells and applications thereof

A technology of tumor stem cells and gene medicine, applied in the field of gene medicine that promotes the differentiation of tumor stem cells, can solve the problems of recurrence and metastasis that plague surgeons, produce tumor tissue treatment resistance, and lack of differentiation of tumor stem cells, so as to improve drug sensitivity, Safe to use, low toxicity and side effects

Inactive Publication Date: 2013-09-11
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AI-Extracted Technical Summary

Problems solved by technology

[0002] Traditional tumor treatment methods include chemotherapy, radiotherapy and surgery, but from the perspective of clinical treatment effects, none of them can completely cure the tumor
Moreover, due to the non-specific killing effect of radiotherapy and chemotherapy, the toxicity to the body is relatively high, and long-term use will cause treatment tolerance of tumor tissues.
The curative effect of surgery...
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The invention provides a gene medicine for promoting the differentiation of tumor stem cells. The gene medicine comprises a recombinant of which the target gene is a Nell-1 gene and can effectively induce the differentiation of the tumor stem cells, inhibit the multiplication of tumor cells, reduce the drug resistance of the tumor cells and improve the drug sensitivity and can be combined with chemical treatment to enhance the chemical treatment effect; and the gene medicine is low in toxic and side effects and safely used. A carrier of the recombinant can be an expression plasmid or a virus carrier, preferably the virus carrier; the virus carrier is preferably selected from one of an adenovirus carrier, a herpes simplex virus carrier, a retroviruse carrier, an adeno associated virus carrier and a slow virus carrier; and most preferably, the virus carrier is the adenovirus carrier.

Application Domain

Genetic material ingredientsAntineoplastic agents +1

Technology Topic

Adeno associate virusSide effect +12


  • Gene medicine for promoting differentiation of tumor stem cells and applications thereof
  • Gene medicine for promoting differentiation of tumor stem cells and applications thereof
  • Gene medicine for promoting differentiation of tumor stem cells and applications thereof


  • Experimental program(4)

Example Embodiment

[0024] Example 1 Nell-1 gene applied to glioma
[0025] The Nell-1 gene sequence was obtained by RT-PCR. After the detection was correct, the full-length gene was amplified by PCR in vitro, and then the amplified product was cloned into an expression plasmid to obtain an expression plasmid (Nell-1) carrying the Nell-1 gene. 1 expression plasmid). The Nell-1 expression plasmid was used to transfect into glioma stem cell line (DA66), and the positive ratio of CD133 in this tumor stem cell line was about 65-70%.
[0026] After G418 screening, a stable and high Nell-1 expression cell line (DA66-Nell-1) was obtained, stained with CD133 antibody, and then analyzed by flow cytometry, such as figure 1 As shown (where DA66 is a complete blank control without any treatment, and DA66-Neo is a blank plasmid transfection), Nell-1 overexpression significantly reduces the expression of CD133, while the transfection of blank plasmid (DA66-Neo) significantly reduces the expression of CD133. The expression of CD133 had little effect, indicating that overexpression of Nell-1 suppressed the expression of CD133.
[0027] DA66-Nell-1 and DA66-Neo were cultured in vitro, and their differentiation was observed. The results are as follows figure 2 As shown, glioma stem cells overexpressed Nell-1, leading to the differentiation of tumor stem cells. Markers related to neural stem cell differentiation (GFAP, MAP2) and bone differentiation (OPN and OCN) were also significantly increased in DA66-Nell-1 ( figure 2 A), at the same time, the proliferation ability of DA66-Nell-1 cells was significantly reduced in vitro ( figure 2 B), indicating that Nell-1 can effectively induce glioma stem cell differentiation and inhibit cancer cell proliferation.
[0028] Male nude mice aged about 6-8 weeks were selected and divided into two groups. DA66-Neo or DA66-Nell-1 cells were subcutaneously injected respectively. After 4 weeks, the tumor tissue was taken and the tissue was stained with HE. The results are as follows: image 3 As shown, the tumorigenic ability of DA66-Nell-1 was significantly less than that of the DA66-Neo control group ( image 3 A). HE staining revealed that tumors formed after injection of Nell-1-overexpressing cells were characterized by differentiation and mineralization ( image 3 B).
[0029] In vitro drug sensitivity assay of DA66-Nell-1 and DA66-Neo cells, the results are as follows Figure 4 As shown, after Nell-1 overexpression in DA66-Nell-1, tumor cells lost their resistance to chemotherapeutic drugs. It can be seen that Nell-1 can not only induce the differentiation of tumor stem cells, but also enhance the sensitivity of tumor stem cells to chemotherapy. Spend.
[0030] Cancers other than gliomas are tested the same way as above, and the test results are similar to gliomas.

Example Embodiment

[0031] The preparation of the recombinant of embodiment 2 target gene is Nell-1
[0032] The Nell-1 gene sequence was obtained by RT-PCR. After the detection was correct, the full length of the gene was amplified by PCR in vitro, and the amplified product clone and adenovirus shuttle plasmid were cut with specific endonuclease to construct a Nell-carrying plasmid. -1 gene shuttle plasmid, then subcloned into pQB1-AdCMV5 (containing adenovirus E1A), co-transfected with QB1-viral DNA, positive virus clones were screened by PCR to obtain Ad-Nell-1 recombinant, amplified, transfected HEK293 cells were transfected, cultured, the Nell-1 gene recombinant adenovirus was roughly divided, purified by ultracentrifugation, sterilized, and obtained.

Example Embodiment

[0033] The preparation of embodiment 3 injection
[0034] The Ad-Nell-1 recombinant obtained in Example 2 was 2×10 15 Virus titer, add normal saline for injection to 1000mL, sterile filter, and dispense into 2mL vials.


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Description & Claims & Application Information

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