Research On Targeted Therapy For Bladder Cancer Based On Ligustilide And Cancer Stem Cells

Bladder cancer is one of the top ten malignant tumors in the world.In 2022,the number of new cases of bladder cancer in China was about 90,000 and the number of deaths was about 40,000,both of which are still on the rise.Due to the low response rate and high recurrence rate,patients with advanced bladder cancer often lack treatment options.As a new treatment method,Chinese monomer has the characteristics of low price and multi-target.Bladder cancer stem cells,as the root cause of high recurrence of bladder cancer,are characterized by high heterogeneity.Therefore,it is necessary to explore a new marker of bladder cancer and the anti-bladder cancer activity of TCM monomers.This is the first study to show that ligustilide exhibited significant anti-bladder cancer activity in vivo and in vitro.Ligustilide induced apoptosis of T24 and EJ bladder cancer cells,controlled the cell cycle in Sub-G1 phase,and significantly inhibited cell proliferation.Ligustilide inhibited the growth of bladder cancer in subcutaneous tumor bearing mice.Ligustilide up-regulated Caspase 8,Bid and BAX,down-regulated NFκB1 and induced apoptosis.Although ligustilide was shown to cause slow growth of bladder cancer,it did not completely inhibit tumor growth.It was found that A01 was significantly overexpressed in bladder cancer stem cells,and the reduction of A01 expression could arrest the cell cycle in S phase,inhibit cell proliferation,and decrease the transcription level of dry factors.Therefore,A01 is a novel marker of bladder cancer stem cells.In conclusion,this study revealed the molecular mechanism of ligustilide inducing apoptosis of bladder cancer cells through mitochondria mediated apoptosis pathway,and identified a novel marker A01 of bladder cancer stem cells,laying a theoretical foundation for precision treatment of bladder cancer.