HYR-2 plays an anti-lung cancer role by regulating PD-L1 and Akkermansia

Lung Cancer

Pharmacol Res. 2020 Jul 17:105086. doi: 10.1016/j.phrs.2020.105086. Online ahead of print.


Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. HYR-2 (Huoxue Yiqi Recipe-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "synopsis of the golden chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways including lung cancer, non-small cell lung cancer and the

expression of PD-L1 in cancer. Then, data about NSCLC downloaded from GEO, TCGA and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 signaling pathway). In vivo and in vitro experiments showed that HYR or HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia.