Mechanism of Polypeptide Extract from Scorpion Venom Combined Rapamycin in Enhancing Autophagy of H22 Hepatoma Cells: an Experimental Study.
- Author:
Qian-qian ZHAO
;
Wei-dong ZHANG
;
Li-cun WU
;
Lu-lu ZHANG
;
Zhao-peng WANG
;
Yue-ying ZHANG
;
Zhao-xia WANG
;
Qing JIA
- Publication Type:Journal Article
- MeSH: Animals; Antineoplastic Combined Chemotherapy Protocols; pharmacology; therapeutic use; Autophagy; drug effects; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Mice; Neoplasm Transplantation; Peptides; Scorpion Venoms; pharmacology; therapeutic use; Sirolimus; pharmacology; therapeutic use
- From: Chinese Journal of Integrated Traditional and Western Medicine 2015;35(7):866-870
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism.
METHODSThe H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay.
RESULTSThe growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05).
CONCLUSIONPESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.