Lentiviral vector-mediated gene transfer combined with cisplatin enhances tumor suppression in human bladder cancer cell lines

Abstract

Purpose

Non-muscle invasive bladder cancer (NMIBC) shows high rates of recurrence and frequently progresses to more advanced stages, such as muscle invasive bladder cancer (MIBC). Repetition of treatment and recurrence are serious burdens and cause severe reduction in the quality of life (QOL) of patients. Thus, a novel therapeutic strategy without high burdens on the patients is an urgent requirement. Consequently, we evaluated tumor growth inhibition in bladder cancer cell lines using a combination of cisplatin (CDDP), one of the prevailing anticancer drugs to treat bladder cancer, and lentiviral vector-mediated gene transfer, where the vector is known to have minimal cytotoxicity.

Methods

Lentiviral vector with tumor suppressor genes including p53, p16, and phosphatase and tensin homology (PTEN) were infected to human bladder cancer cell lines, UMUC3 and T24, followed by CDDP treatment.

Results

The transduction of the p53, p16, or PTEN gene was equivalent to the antitumor efficacy of CDDP against bladder cancer cells. Furthermore, lentiviral vector-mediated transduction of tumor suppressive genes in combination with CDDP showed superior antitumor effects relative to individual treatment strategies with the vector or CDDP alone.

Conclusion

Lentiviral vector-mediated gene transduction is a promising alternative to the existing therapy in treating bladder cancer. The current protocol of CDDP-based chemotherapy may be replaced in the future. Moreover, the combination of gene therapy and chemotherapy may be an effective treatment for bladder cancer.