Arctigenin enhances the sensitivity of cisplatin resistant colorectal cancer cell by activating autophagy.

Arctigenin is the active content of arctium lappa that present anti-cancer abilities in various carcinomas. However, its role and underlying mechanism in drug-resistant colorectal cancer cells has not been addressed. The present study used SW480 and SW620 to established cisplatin-resistant colorectal cancer cell lines, and explored the impact of arctigenin on these cells. Arctigenin at 100 μM significantly inhibited cell proliferation of cisplatin treated R-SW480 and R-SW620 cells as compared with cells treated with cisplatin alone. Arctigenin elevates cell apoptosis, up-regulated pro-apoptotic protein cleaved-caspase-3 and caspase-9 expression level in cisplatin treated R-SW480 and R-SW620 cells. Additionally, arctigenin triggered autophagy and promoted LC3-Ⅱ and p65 expression, while inhibited LC3-Ⅰexpression. Arctigenin impeded the IC₅₀ of not only cisplatin but also oxaliplatin, doxorubicin and Paclitaxel of R-SW480 and R-SW620 cells. More importantly, the mRNA expression of multi drug resistance 1 (MDR1) and protein expression of pgp were significantly inhibited by arctigenin administration. Taken together, arctigenin has the potential in sensitize colorectal cancer cells by activating autophagy, which induced cell apoptosis and inhibited cell growth. Our study revealed that arctigenin has the potential for colorectal cancer treatment and may be useful in adjuvant chemotherapy.