Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 15 1 2025 04 15 PTEN and p53 Combined Gene Therapy Promote Apoptosis and Chemosensitivity to Oxaliplatin in Colorectal Cancer: An In Vitro Study 154 161 10.34172/apb.43371 EN Narjes Nakhaee https://orcid.org/0000-0002-6013-7186 Sirous Zeinali https://orcid.org/0000-0002-2080-9582 Mahboubeh Kabiri https://orcid.org/0000-0003-3123-1365 Ladan Teimoori-Toolabi https://orcid.org/0000-0002-6588-9774 Journal Article 10.34172/apb.43371 2024 06 30 2025 02 03 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.