Anti-lung cancer mechanisms of diterpenoid tanshinone via endoplasmic reticulum stress-mediated apoptosis signal pathway.
10.19540/j.cnki.cjcmm.20180725.002
- Author:
Zhao-Huan LOU
1
;
Rong-Man XIA
1
;
Xiao-Juan LI
1
;
Ru-Bin CHENG
1
;
Ke-Ding SHAO
1
;
Guang-Ji ZHANG
1
Author Information
1. Zhejiang Chinese Medical University, Hangzhou 310053, China.
- Publication Type:Journal Article
- Keywords:
IRE1α/caspase 12 pathway;
Salviae Miltiorrhizae Radix et Rhizoma;
diterpenoid tanshinone;
endoplasmic reticulum stress;
lung cancer
- MeSH:
Animals;
Apoptosis;
Cell Line, Tumor;
Diterpenes, Abietane;
Endoplasmic Reticulum Stress;
Humans;
Lung Neoplasms;
Mice;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2018;43(24):4900-4907
- CountryChina
- Language:Chinese
-
Abstract:
At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.
