Midkine Promoter-Driven Lentiviral Delivery of PTEN for Human Bladder Cancer

Abstract

Background: Non-muscle-invasive bladder cancer has a high recurrence rate, necessitating the development of novel therapeutic strategies. PTEN is a tumor suppressor that regulates cell proliferation and survival. The Midkine (MK) promoter, which is selectively active in cancer cells, offers a promising approach to gene therapy. This study investigated MK promoter-driven PTEN delivery using lentiviral vectors for selective bladder cancer treatment.

Methods: Lentiviral vectors expressing PTEN under the MK promoter (MKp-PTEN) or cytomegalovirus promoter (CMV-PTEN) were introduced into bladder cancer (5637, T24, and 253J) and non-malignant (PNT1A) cell lines. Cell viability was assessed using the CCK-8 assay, and statistical analysis was performed using analysis of variance.

Results: MKp-PTEN significantly inhibited the proliferation of bladder cancer cells, especially 253J and 5637 cells, with a stronger effect than CMV-PTEN. In non-malignant PNT1A cells, MKp-PTEN caused a minor, statistically insignificant reduction in viability compared with CMV-PTEN. These findings provide preliminary, proof-of-concept evidence that MK promoter-driven PTEN expression is a promising pre-clinical strategy for a tumor-specific therapy for bladder cancer.