摘要
Objective:Huachansu injection(HCSI),a promising anti-cancer Chinese medicine injection,has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer(CRC)patients.The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan(CPT-11).Methods:To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11,we measured changes in the biological behavior of LoV o cells in vitro,and anti-tumor effects in LoV o cell xenograft nude mice models in vivo.Meanwhile,the effect of HCSI on intestinal toxicity and the uridine diphosphateglucuronosyltransferase 1A1(UGT1A1)expression was investigated in the CPT-11-induced colitis mouse model.Subsequently,we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3(OATP1B3)in HepG 2 cells.Results:The combination index(CI)results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect(CI<1),which significantly suppressing the LoV o cell migration,enhancing G2/M and S phase arrest,and inhibiting tumor growth in vivo.Additionally,the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model,while the increased expression of UGT1A1 in HepG 2 cells and in mouse was observed.Conclusion:The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect.The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components.The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes.
基金
the award from Pudong Commission of Science and Technology and Economy and Informatization(No.PKJ2019-Y04)
Pudong New Area Health Commission Health Research Project(No.PW2021E-03)
Traditional Chinese Medicine Inheritance and Scientific and Technological Innovation Project of Shanghai Municipal Health Commission(No.ZYCC2019017)for financial support of this study。
