Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo.
10.1016/j.joim.2025.06.006
- Author:
Bo JIANG
1
;
Zhao-Yang MENG
2
;
Yu-Jie HU
3
;
Jun-Jun CHEN
3
;
Ling ZONG
3
;
Ling-Yan XU
3
;
Xiang-Qi ZHANG
3
;
Jing-Xian ZHANG
3
;
Yong-Long HAN
4
,
5
Author Information
1. Shanghai Changning Mental Health Center, East China Normal University, Shanghai 200335, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
2. Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
3. Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
4. Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China. Electronic address: yonglongh@
5. com.
- Publication Type:Journal Article
- Keywords:
Bufadienolides;
Colorectal cancer;
Huachansu injection;
Irinotecan;
UGT1A1
- MeSH:
Irinotecan/therapeutic use*;
Animals;
Glucuronosyltransferase/genetics*;
Humans;
Colorectal Neoplasms/metabolism*;
Drugs, Chinese Herbal/therapeutic use*;
Mice, Nude;
Mice;
Up-Regulation/drug effects*;
Male;
Xenograft Model Antitumor Assays;
Mice, Inbred BALB C;
Hep G2 Cells;
Cell Line, Tumor;
Intestines/drug effects*;
Amphibian Venoms
- From:
Journal of Integrative Medicine
2025;23(5):576-590
- CountryChina
- Language:English
-
Abstract:
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 LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 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 HepG2 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 LoVo 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 HepG2 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. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
