GPR30 Activation Promotes the Progression of Gastric Cancer and Plays a Significant Role in the Anti-GC Effect of Huaier.

Autor: Wang XF; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Affiliated Cixi Hospital, Wenzhou Medical University (Cixi People's Hospital), Ningbo 315300, China., Hu C; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China., Mo SW; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China., Xu JL; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China., Liu Y; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China., Xu HD; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China., Yuan L; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China., Huang L; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China., Yu JF; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China., Cheng XD; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.; Diagnosis and Therapy Center of Upper Gastrointestinal Tumor in Zhejiang Province, Hangzhou 310022, China., Xu ZY; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.; Diagnosis and Therapy Center of Upper Gastrointestinal Tumor in Zhejiang Province, Hangzhou 310022, China.
Jazyk: angličtina
Zdroj: Journal of oncology [J Oncol] 2022 Jan 19; Vol. 2022, pp. 2410530. Date of Electronic Publication: 2022 Jan 19 (Print Publication: 2022).
DOI: 10.1155/2022/2410530
Abstrakt: Gastric cancer (GC) is one of the most common types of cancer. The n-butanol extract of Huaier (NEH) is the alcohol-soluble part extracted by the systematic solvent method, which is effective against gastric cancer (GC). However, the mechanism of action of NEH remains unclear. In this study, we aim to evaluate the clinical relevance of GPR30 expression in GC patients and the role of the GPR30/PI3K/AKT signalling pathway in the anti-GC effect of NEH. The expression of GPR30 was examined using immunohistochemistry. Cell counting kit 8 (CCK-8) assay, wound healing, and transwell experiments were used to investigate the viability, migration, and invasion of gastric cancer cells. Western blotting was used to detect the expression of GPR30 and its downstream signalling molecules of the PI3K/AKT signalling pathway. Gastric cancer patient-derived xenografts (PDX) mouse model was used to evaluate the antitumor effect of NEH in vivo . In addition, the graded doses and the maximum tolerated dose of NEH were administered intraperitoneally into the mice for acute toxicity test. We demonstrate that GPR30 expression in GC tissues was significantly higher than that in corresponding adjacent noncancerous tissues and the expression of GPR30 was correlated with a poor prognosis in GC patients. Moreover, GPR30 expression was involved in the migration and invasion of GC cells in vitro. Additionally, we found that NEH can suppress the growth of GC in patient-derived xenograft tumors in vivo. Furthermore, NEH inhibited the proliferation, migration, and invasion in GC cells in a concentration-dependent manner through inhibiting the GPR30-mediated PI3K/AKT signalling pathway in vitro. Acute toxicity test showed that NEH caused no toxic reaction or death and the maximum tolerated dose of NEH in mice was greater than 1600 mg/kg. Our results demonstrate that the high expression of GPR30 is an independent factor of poor prognosis in patients with GC and NEH could be a new agent for the treatment of gastric cancer.
Competing Interests: The authors declare that they have no conflicts of interest.
(Copyright © 2022 Xiao-feng Wang et al.)
Databáze: MEDLINE
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