JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (9): 13-18.doi: 10.6040/j.issn.1671-7554.0.2015.281

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Effects of nitidine chloride on the proliferation and apoptosis of prostate cancer PC-3 cells

CHENG Xiangyu1, XING Rui2, XING Zhaoquan1, GUO Zhaoxin1, GUO Xiaoyu3, SU Jing3, MENG Liwei1, LIU Zhaoxu1,3   

  1. 1. Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Urology, Peoples Hospital of Linyi, Linyi 251500, Shandong, China;
    3. School of Nursing, Shandong University, Jinan 250012, Shandong, China
  • Received:2015-03-16 Online:2015-09-10 Published:2015-09-10
  • Contact: 刘照旭。E-mail:zhaoxvl@sdu.edu.cn E-mail:zhaoxvl@sdu.edu.cn

Abstract: Objective To evaluate the effects of nitidine chloride on the proliferation and apoptosis of prostate cancer cells PC-3 in vitro. Methods MTT, scratch migration and Transwell were used to examine the changes in the proliferation and invasions of human prostate cancer cell PC-3 after nitidine chloride treatment. Flow cytometry was used to examine the changes in cell apoptosis of PC-3. Immunoblot analysis was adopted to detect the expression of AKT/mTOR, Bcell-associated x protein (Bax) and Bcell lymphoma-2 (Bcl-2). A specific PI3K inhibitor, LY294002, was used to evaluate the influence of prostate cancer cells by inhibiting AKT pathway. Results Nitidine chloride inhibited the proliferation and invasion of PC-3 cells in a dose-dependent manner (P<0.01). Nitidine chloride inhibited AKT and mTOR pathways phosphorylation, accompanied by up-regulation of Bax, and down-regulation of Bcl-2. Nitidine chloride significantly increased the ratio of Bax/Bcl-2 (P<0.01), to induce prostate cancer cells apoptosis. Furthermore, combined use of LY294002 inhibited AKT pathway, which could enhance the anti-proliferation and anti-invasion effectsof nitidine chloride. Conclusion Nitidine chloride can suppress the proliferation, migration, invasion and induce the apoptosis of prostate cancer cells in vitro. Nitidine chloride also plays a role in anti-cancer via inhibiting AKT/mTOR pathway phosphorylation, which implies that nitidine chloride may be a promising therapeutic drug for prostate cancer.

Key words: Prostate neoplams, Apoptosis, Nitidine chloride, AKT /mTOR pathway, Cell metastasis

CLC Number: 

  • R737.25
[1] Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014[J]. CA Cancer J Clin, 2014, 64(1): 9-29.
[2] Du LB, Li HZ, Wang XH, et al. Analysis of cancer incidence in Zhejiang cancer registry in China during 2000 to 2009[J]. Asian Pac J Cancer Prev, 2014, 15(14): 5839-5843.
[3] Edlind MP, Hsieh AC. PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance[J]. Asian J Androl, 2014, 16(3): 378-386.
[4] Sun M, Zhang N, Wang X, et al. Nitidine chloride induces apoptosis, cell cycle arrest, and synergistic cytotoxicity with doxorubicin in breast cancer cells[J]. Tumour Biol, 2014, 35(10): 10201-10212.
[5] Fang Z, Tang Y, Jiao W, et al. Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway[J]. Food Chem Toxicol, 2013, 60: 246-251. doi: 10.1016/j.fct.2013.07.062. Epub 2013 Jul 31.
[6] Kang M, Ou H, Wang R, et al. The effect of nitidine chloride on the proliferation and apoptosis of nasopharyngeal carcinoma cells[J]. J BUON, 2014, 19(1): 130-136.
[7] Fang Z, Tang Y, Jiao W, et al. Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer[J]. Food Chem Toxicol, 2014, 66: 210-216. doi: 10.1016/j.fct.2014.01.049. Epub 2014 Feb 5.
[8] Chen J, Wang J, Lin L, et al. Inhibition of STAT3 signaling pathway by nitidine chloride suppressed the angiogenesis and growth of human gastric cancer[J]. Mol Cancer Ther, 2012, 11(2): 277-287.
[9] Pan X, Han H, Wang L, et al. Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway[J]. Cancer Lett, 2011, 313(2): 181-191.
[10] Brugge J, Hung MC, Mills GB. A new mutational AKTivation in the PI3K pathway[J]. Cancer Cell, 2007, 12(2): 104-107.
[11] Liu K, Park C, Li S, et al. Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2[J]. Carcinogenesis, 2012, 33(7): 1406-1411.
[12] Hsieh TC, Lin CY, Lin HY. AKT/mTOR as novel targets of polyphenol piceatannol possibly contributing to inhibition of proliferation of cultured prostate cancer cells[J]. ISRN Urol, 2012, 2012: 272697. doi: 10.5402/2012/272697. Epub 2012 Apr 3.
[13] Kinkade CW, Castillo-Martin M, Puzio-Kuter A, et al. Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model[J]. J Clin Invest, 2008, 118(9): 3051-3064.
[14] Fresno Vara JA, Casado E, de Castro J, et al. PI3K/Akt signalling pathway and cancer[J]. Cancer Treat Rev, 2004, 30(2): 193-204.
[15] 季恩飞, 刘学文. p38MAPK信号通路抑制剂对NMDA诱导的体外培养的皮层神经元损伤的保护作用及机制[J]. 山东大学学报:医学版, 2013, 51(11): 10-15. JI Enfei, LIU Xuewen. Protective effects and mechanism of p38MAPK signaling pathway inhibitors on NMDA-induced primary cultured cortical neurons injury in vitro[J]. Journal of Shandong University: Health Sciences, 2013, 51(11): 10-15.
[16] Williams MM, Cook RS. Bcl-2 family proteins in breast development and cancer: could Mcl-1 targeting overcome therapeutic resistance?[J]. Oncotarget, 2015, 6(6):3519-3530.
[17] Li B, Yadav RK, Jeong GS, et al. The characteristics of Bax inhibitor-1 and its related diseases[J]. Curr Mol Med, 2014, 14(5): 603-615.
[18] Hoang TC, Bui TK, Taguchi T, et al. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein[J]. J Exp Clin Cancer Res, 2010, 29: 165. doi: 10.1186/1756-9966-29-165.
[19] Xu GP, Zhao W, Zhuang JP, et al. Matrine inhibits the growth and induces apoptosis of osteosarcoma cells in vitro by inactivating the Akt pathway[J]. Tumour Biol, 2015, 36(3):1653-1659.
[20] Umesalma S, Nagendraprabhu P, Sudhandiran G. Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells[J]. Mol Cell Biochem, 2015, 399(1-2): 303-313.
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