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PTEN and p53 Combined Gene Therapy Promote Apoptosis and Chemosensitivity to Oxaliplatin in Colorectal Cancer: An In
Narjes Nakhaee1, Sirous Zeinali2, Mahboubeh Kabiri1
1Department of Biotechnology, Faculty of Science, Tehran University, Tehran, Iran.
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.
Insights
Combining PTEN and p53 gene therapy shows synergistic anticancer effects in colorectal cancer cells. This dual-gene approach enhances apoptosis and increases sensitivity to chemotherapy, offering a promising new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Gene therapy is an evolving and promising approach for cancer treatment.
- PTEN and p53 proteins are known to possess significant antitumor properties.
- The combined therapeutic potential of up-regulating both PTEN and p53 genes remains largely unexplored, particularly in colorectal cancer.
Purpose of the Study:
- To investigate the combined therapeutic potential of PTEN and p53 gene up-regulation in colorectal cancer (CRC) cells.
- To assess the synergistic anticancer impact of co-expressing PTEN and p53.
- To evaluate the effect of combined PTEN and p53 expression on CRC cell apoptosis, cell cycle, and chemosensitivity.
Main Methods:
- SW480 colorectal cancer cell line was transfected with PTEN, p53, and blank vectors.
- Cell viability was assessed using MTT assays.
- Apoptosis and drug sensitivity were analyzed via flow cytometry.
- Gene expression changes were quantified using real-time PCR.
Main Results:
- PTEN demonstrated a greater capacity to induce apoptosis than p53 in SW480 cells.
- Co-expression of PTEN and p53 exhibited a synergistic anticancer effect.
- Combined gene expression significantly altered genes related to cell cycle regulation and apoptosis.
- Co-expression of PTEN and p53 enhanced the sensitivity of CRC cells to oxaliplatin.
Conclusions:
- Targeting both PTEN and p53 tumor suppressor genes via gene therapy presents a potent therapeutic strategy for colorectal cancer.
- This dual-gene approach may also be applicable to the treatment of other cancer types.
- The synergistic action of PTEN and p53 highlights their importance in cancer therapy.
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