Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway.
10.19540/j.cnki.cjcmm.20230518.701
- Author:
Xin-Jun DAI
1
;
Yan LONG
2
;
Bo ZOU
2
;
Li-Tong WU
2
;
Jun-Feng QIU
2
;
Yong-Rong WU
2
;
Zhe DENG
2
;
Yong-Li WANG
2
;
Qing ZHOU
3
;
Xue-Fei TIAN
4
Author Information
1. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine Changsha 410208, China Liuyang Hospital of Traditional Chinese Medicine Affiliated to Hunan University of Chinese Medicine Changsha 410300, China.
2. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine Changsha 410208, China.
3. Department of Andrology, the First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007, China.
4. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine Changsha 410208, China Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prescription and Transformation, Hunan University of Chinese Medicine Changsha 410208, China Key Laboratory of Tumor Prevention Mechanism of Traditional Chinese Medicine Changsha 410208, China.
- Publication Type:Journal Article
- Keywords:
AR/mTOR signaling pathway;
Xihuang Pills;
apoptosis;
prostate cancer
- MeSH:
Humans;
Male;
Mice;
Rats;
Animals;
Caspase 3/metabolism*;
Mice, Nude;
Cell Line, Tumor;
Rats, Sprague-Dawley;
Signal Transduction;
TOR Serine-Threonine Kinases/metabolism*;
Prostatic Neoplasms/pathology*;
Cell Proliferation;
Apoptosis;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Mammals/metabolism*
- From:
China Journal of Chinese Materia Medica
2023;48(15):4147-4155
- CountryChina
- Language:Chinese
-
Abstract:
Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.
