Impact of carbamazepine on SMARCA4 (BRG1) expression in colorectal cancer: modulation by KRAS mutation status

卡马西平对结直肠癌 SMARCA4 (BRG1) 表达的影响:受 KRAS 突变状态的调节

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作者:Aaron Shaykevich, Danbee Chae, Isaac Silverman, Jeremy Bassali, Netanel Louloueian, Alexander Siegman, Gargi Bandyopadhyaya, Sanjay Goel, Radhashree Maitra

Abstract

SMARCA4 is a gene traditionally considered a tumor suppressor. Recent research has however found that SMARCA4 likely promotes cancer growth and is a good target for cancer treatment. The drug carbamazepine, an autophagy inducer, was used on colorectal cancer cell lines, HCT1116 and Hke3 (KRAS mutant and wildtype). Our study finds that Carbamazepine affects SMARCA4 levels and that this effect is different depending on the KRAS mutation status. This study analyzes the effect of carbamazepine on early-stage autophagy via ULK1 as well as simulates the docking of carbamazepine on KRAS, depending on the mutation status. Our study highlights the therapeutic uses of carbamazepine on cancer, and we propose that carbamazepine in conjunction with other chemotherapies may prove useful in targeting KRAS-mutated colorectal cancer.

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