XIAOPI formula is a national approved drug prescribed to patients with high
breast cancer risk. Previously we demonstrated that XIAOPI formula could inhibit
breast cancer metastasis via suppressing CXCL1 expression, and postulated that "autophagy in
cancer" might be one of its most core anti-
cancer mechanisms. However, whether XIAOPI formula could be simultaneously applied with chemodrugs and their synergistic mechanisms are still remained unknown. In the present study, XIAOPI formula at non-cytotoxic doses could synergistically enhance the chemosensitivity of
breast cancer cells MDA-MB-231 and MCF-7. We found that
rapamycin-induced autophagy could reduce the chemosensitivity of
breast cancer cells to XIAOPI formula, and the autophagy suppression and chemosensitizing activity of this formula was CXCL1-dependent. The evidence came from that XIAOPI formula was associated with a lower expression of CXCL1 combined with either
rapamycin or
taxol alone. Besides, the inhibitory effect of XIAOPI formula on the LC3-II and ABCG2 signals was weakened following CXCL1 over-expression, whereas P62 upregulation induced by XIAOPI formula was re-declined. A high throughput - qPCR (HT-qPCR) assay identified
HMGB1 as the main autophagic target of XIAOPI formula in chemosensitizing
breast cancer. and furhter validation suggested XIAOPI formula exerted chemosensitivity mainly via CXCL1/
HMGB1 autophagic axis. Finally, we generated both mice and zebrafish
xenotransplantation models bearing MDA-MB-231
breast cancer cells, and found that XIAOPI formula safely enhanced in vivo
taxol chemosensitivity on
breast cancer. Taken together, XIAOPI formula is a potential adjuvant drug via inhibiting CXCL1/
HMGB1-mediated autophagy for
breast cancer treatment with good safety.