PTEN and p53 Combined Gene Therapy Promote Apoptosis and Chemosensitivity to Oxaliplatin in Colorectal Cancer: An In Vitro Study

PTEN 和 p53 联合基因疗法促进结直肠癌细胞凋亡并提高其对奥沙利铂的化疗敏感性:一项体外研究

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Abstract

PURPOSE: Cancer is a complex condition and gene therapy has evolved as a promising method for cancer treatment. Studies have demonstrated that PTEN and p53 proteins have remarkable antitumor effects but combined up-regulation of both PTEN and p53 genes has not been reported. We thus investigated their therapeutic potential in colorectal cancer (CRC) cells. METHODS: PTEN, p53, and blank vectors were purchased from Addgene, and transfected in SW480 cell line. Cell viability and apoptosis was assayed by MTT and flow cytometric analysis respectively. Real-time PCR assay was applied to assess changes in the expression of genes. To evaluate the effect on drug sensitivity of transfected cells, flow cytometric analysis was conducted. RESULTS: PTEN are more able to induce apoptosis than p53 in SW480 and PTEN and p53 demonstrated a synergistic anticancer impact. Further tests showed that both genes increased the change in the expression of genes related to cell cycle and apoptotic factors. Co-expression of these genes can also increase the susceptibility of CRC cells to the chemotherapeutic agent oxaliplatin. CONCLUSION: According to our findings, cancer gene therapy targeting two tumor suppressors, like PTEN and p53 genes, might be a potent therapeutic approach for treating colorectal and other cancers.

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