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Application of RBMS3 as molecular target for tumor drug resistance detection, treatment and prognosis

A tumor and drug resistance technology, applied in measurement devices, analytical materials, and microbial determination/inspection, etc., can solve the problems of limited clinical application effect of PRI-724, lack of molecular targeting indicators, etc., to achieve good tumor treatment effect, improve Accuracy and limitations, the effect of strong stability

Active Publication Date: 2018-08-17
SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, the small molecule inhibitor PRI-724 (ICG-001, which is mostly used in in vitro experimental research) that inhibits the combination of CBP and β-catenin is currently being used in clinical trials of various tumors. However, due to the lack of specific molecular Targeted indicators, the clinical application effect of PRI-724 is greatly limited

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  • Application of RBMS3 as molecular target for tumor drug resistance detection, treatment and prognosis
  • Application of RBMS3 as molecular target for tumor drug resistance detection, treatment and prognosis
  • Application of RBMS3 as molecular target for tumor drug resistance detection, treatment and prognosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1. RBMS3 is missing in various tumors and leads to tumor resistance

[0064] (1) TCGA database analysis and MTT experiment to screen target genes

[0065] Method: Through analyzing the high-throughput sequencing data of single nucleotide polymorphism (SNP) copy number in 33 tumors in the TCGA public database, the tumor types with significant deletion in the short arm of chromosome 3 (Chr3p) were screened out, and Through survival prognostic analysis, analyze the correlation between 3p deletion and the overall survival rate and recurrence of tumor patients. Single factor, COX regression and multivariate analysis were used to screen chromosomal regions related to patient recurrence. In EOC cell lines A2780 and SKOV3, the corresponding siRNA was used to inhibit 368 genes encoded by Chr3p, respectively, and the cytotoxic effect of cisplatin was tested after inhibiting the corresponding genes alone.

[0066] Results: The analysis results showed that 13 tumors including ov...

Embodiment 2

[0080] Example 2. In in vivo experiments, RBMS3 deletion / low expression can enhance the cisplatin resistance of epithelial ovarian cancer

[0081] (1)Patient-derived xenografts model (PDX model) construction

[0082] Methods: The 15 fresh EOC tissues collected in Example 1 were planted into the back of NOD / Shi-scid / IL-2Rγnull (NOG) mice subcutaneously and named OV#1, OV#2...OV#, respectively 15. When the subcutaneous tumor can be touched, divide each group of NOG groups into two groups, and intraperitoneally inject PBS or cisplatin (CDDP, 5mg / kg) respectively, record the tumor size every week and draw the corresponding tumor growth curve. Two samples of OV#2 and OV#11 were selected in the RBMS3-deletion group and RBMS3-non-deletion group, and the subcutaneous tumors formed were taken out and the primary cells were isolated and named OV-2 and OV-11. FISH and Western blot experiments were used to verify the genome and protein expression levels of RBMS3 in OV-2 and OV-11.

[0083] Res...

Embodiment 3

[0094] Example 3. In in vitro experiments, the lack / low expression of RBMS3 can enhance the chemotherapy resistance of epithelial ovarian cancer to cisplatin.

[0095] (1) In vitro drug resistance experiments verify the effect of RBMS3 deletion / low expression on the drug resistance of epithelial ovarian cancer cells to cisplatin

[0096] Methods: Construct cell lines OV-2RBMS3si#1 and OV-2RBMS3si#2 with low RBMS3 expression in OV-2 primary cells, and construct cell lines SKOV3RBMS3gRNA#1 and OV-2RBMS3gRNA#2 with RBMS3 knockout in SKOV3 cells , Western blot verified the expression of RBMS3. Annexin V flow cytometry was used to detect the apoptotic ratio of RBMS3 deletion / low expression in Vehicle control or Cisplatin (5μM) treatment. Plate clone formation experiment was used to detect the growth of RBMS3 deletion / low expression in Vehicle control or Cisplatin (5μM) treatment. The half inhibitory concentration (IC50) of each group of cells was measured to reflect the effect of RBMS...

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Abstract

The invention discloses application of RBMS3 as a molecular target for tumor drug resistance detection, treatment and prognosis. Inventors find that RBMS3 deletion can promote tumor cisplatin-resistance and tumor recurrence. In the prior art, most tumor therapeutic schedules are surgical resection with adjuvant chemotherapy, and chemotherapy resistance becomes an important factor affecting the prognosis of tumor patients. A specific molecular marker is disclosed and can be used as an important molecular marker for predicting tumor drug resistance. The target gene can be detected at DNA level,and DNA is stronger in stability than RNA or proteins, and can improve the accuracy and limitation of diagnosis. A targeted therapeutic schedule is provided for the treatment of the tumor patients. Abetter therapeutic effect on patients with no RBMS3 deletion tumors can be obtained by use of cisplatin alone; and a better therapeutic effect on patients with RBMS3 deletion tumors can be obtained bycombined use of cisplatin and PRI-724.

Description

Technical field [0001] The present invention relates to the application of RBMS3 as a molecular target for tumor drug resistance detection, treatment and prognosis. Background technique [0002] Ovarian cancer is one of the tumors with the highest mortality in gynecological tumors, among which epithelial ovarian cancer (Epithelial Ovarian Cancer, EOC) is the most common tumor type. The current treatment plan for EOC is surgical resection (cell decompression) combined with platinum-based chemotherapy. Although more than 80% of EOC patients have a good remission response after receiving platinum-based chemotherapy, more than 75% of patients will develop resistance to platinum-based drugs and cause tumor recurrence, resulting in the 5-year survival of EOC patients The rate is only 30%. Therefore, it is a very important research direction and development field to explore the molecular regulation mechanism of tumor resistance and find the targeted regulation molecule. [0003] The mo...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886C12Q2600/106C12Q2600/118C12Q2600/156G01N33/574G01N33/57415G01N33/57438G01N33/57449
Inventor 李隽宋立兵吴阁艳朱金容胡雅梦谭展瑶曹丽雪
Owner SUN YAT SEN UNIV
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