Effect of Squalene Synthase on Malignant Phenotypes and Anti-Cancer Effect of Celastrol on Prostate Cancer Cells

Abstract

Background: Prostate cancer (PC) is one of the most common malignant tumors, and the effect of celastrol on squalene synthase (SQS) in PC is unknown. This study aimed to investigate the effect of celastrol on SQS in PC. Methods: The protein expression was detected by Western blot. Cell proliferation capacity was detected by cell counting kit-8 (CCK-8) kit (450 nm optical density values). Cell scratch (wounding healing rate) and transwell assays (migration cells number) detected the cells migration abilities. Messenger RNA (mRNA) expression was detected using a real-time polymerase chain reaction test. Results: Celastrol decreased the expression of SQS in PC cells, and the knockdown of the SQS-encoding gene farnesyl-diphosphate farnesyltransferase 1 (fdft1) with and without celastrol treatment decreased PC cell proliferation and migration abilities. Furthermore, overexpression of the fdft1 gene attenuated the proliferation and migration abilities of PC-3 cells. Treatment with celastrol with fdft1 gene overexpression can still decrease the proliferation and migration abilities of PC-3 cells. Conclusion: This study verified that celastrol decreases the proliferation and migration abilities of PC-3 and Lymph Node Carcinoma of the prostate (LNCaP) cells and revealed that celastrol reduces SQS expression. The results indicate that the inhibitory effect of celastrol on the malignant phenotypes of PC cells is partly dependent on SQS, and SQS is involved in the malignant behaviour of PC cells. Furthermore, there may be a dual effect dependent on the SQS protein expression level on the malignant phenotypes of PC cells.