Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer (PCa) is a prevalent malignancy with high recurrence and therapy resistance rates.
• Novel therapeutic strategies are urgently needed for effective PCa treatment.
• The sonic hedgehog (SHH) signaling pathway is implicated in various cancers.

Purpose of the Study:

• To investigate the anti-cancer effects of tegaserod maleate (TM) on prostate cancer cells.
• To elucidate the underlying molecular mechanisms of TM's action in PCa.
• To evaluate TM as a potential therapeutic agent for prostate cancer.

Main Methods:

• In vitro assays assessing proliferation, colony formation, migration, invasion, cell cycle arrest, and apoptosis of PCa cells.
• In vivo studies using a cell-derived xenograft (CDX) mouse model to evaluate TM's effect on tumor growth.
• Western blot analysis to examine the expression of GLI2 and downstream targets within the SHH signaling pathway.

Main Results:

• Tegaserod maleate (TM) significantly inhibited PCa cell proliferation, colony formation, migration, and invasion in vitro.
• TM treatment led to cell cycle arrest and induced apoptosis in prostate cancer cells.
• In vivo, TM suppressed tumor growth in a CDX mouse model.
• TM exerted its anti-tumor effects by downregulating GLI2 and its downstream targets, thereby inhibiting the SHH signaling pathway.

Conclusions:

• Tegaserod maleate (TM) demonstrates potent anti-prostate cancer activity through the inhibition of the SHH signaling pathway.
• TM effectively suppresses PCa cell proliferation, invasion, and tumor growth.
• TM represents a promising novel therapeutic agent for prostate cancer treatment.