Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Peiyu Lin Xiyue Yang Linghui Wang Xin Zou Lingli Mu Cangcang Xu Xiaoping Yang
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제28권 제3호, 219~227쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2024.05.01

국문 초록

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was de-signed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at mi-cromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results sug-gest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

목차

INTRODUCTION

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RESULTS

DISCUSSION

키워드

Artesunate Lipogenesis Metformin Urinary bladder neoplasms