AUTHOR=Zheng Dandan , Zhu Yu , Shen Yili , Xiao Sisi , Yang Lehe , Xiang Youqun , Dai Xuanxuan , Hu Wanle , Zhou Bin , Liu Zhiguo , Zhao Haiyang , Zhao Chengguang , Huang Xiaoying , Wang Liangxing TITLE=Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.605184 DOI=10.3389/fcell.2020.605184 ISSN=2296-634X ABSTRACT=Background

Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC.

Methods

Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice.

Results

Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model.

Conclusion

The results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy.