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

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.