Effect of Icaritin on Proliferation and Apoptosis of NCI-H446 Cells_West China Medical Journal

Authors：

 WANGLu ¹ , WANGWen-zhi ¹ , XUJian ¹ , XIAJin ² ,  LIANGZong-an ²

1. Department of Internal Medicine, West China Fourth Hospital;
2. Department of Respiratory Medicine, West China Hospital;Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LIANGZong-an, Email: liang.zongan@163.com

Keywords：

Icaritin; NCI-H446 cells; Proliferation; Apoptosis; Janus kinase 2/signal transducers and activators of transcription 3

DOI：

10.7507/1002-0179.20150404

Video：

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Objective To investigate the effect of icaritin on the small cell lung cancer cell lines NCI-H446 and its mechanism. Methods The NCI-H446 cells at logarithmic growth phase were divided into control and icaritin groups. The cells in the control group were normally treated and cells in the icaritin group were incubated with icaritin (8 μmol/L). Thiazole blue and flow cytometry were used to examine the proliferation and apoptotic changes in the two groups 48 hours after incubation respectively. Gene expression of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) were detected by real-time quantitative polymerase chain reaction. The changes of JAK2, STAT3, phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3), Bax and BCL-2 protein were detected by Western blotting. Results Compared with the control group, the proliferation rate of NCI-H446 cells in the icaritin group was significantly lower (P<0.05), but the apoptotic rate of NCI-H446 cells in the icaritin group was significantly higher (P<0.05). After the treatment with icaritin, the expression of JAK2 and STAT3 mRNA had no obvious differences. The Western blotting results showed that there was no significant changes in total JAK2, STAT3 protein (P>0.05), but an increasing trend in p-JAK2, p-STAT3 and Bax was observed with the decreasing of BCL-2 (P<0.05). Conclusion Icaritin can inhibit the proliferation and promote the apoptosis of NCI-H446 cells and the effect may be achieved through JAK2/STAT3 signal transduction pathway.

Citation： WANGLu, WANGWen-zhi, XUJian, XIAJin, LIANGZong-an. Effect of Icaritin on Proliferation and Apoptosis of NCI-H446 Cells. West China Medical Journal, 2015, 30(8): 1401-1405. doi: 10.7507/1002-0179.20150404 Copy

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13.	Ye HY, Lou YJ. Estrogenic effects of two derivatives of icaritin on human breast cancer MCF-7 cells[J]. Phytomedicine, 2005, 12(10):735-741.
14.	Huang X, Zhu D, Lou Y. A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells[J]. Eur J Pharmacol, 2007, 564(1/2/3):26-36.
15.	Sun F, Indran IR, Zhang ZW, et al. A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants[J]. Carcinogenesis, 2015, 36(7):757-768.
16.	Zhu S, Wang Z, Li Z, et al. Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3[J]. Oncotarget, 2015, 6(12):10460-10472.
17.	Li S, Priceman SJ, Xin H, et al. Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma[J]. PLoS One, 2013, 8(12):e81657.

1. Brown DB, Ma MK, Battafarano RJ, et al. Endovascular lung perfusion using high-dose cisplatin:uptake and DNA adduct formation in an animal model[J]. Oncol Rep, 2004, 11(1):237-243.
2. 廖晖. 经NO-cGMP-PDE5通路治疗勃起功能障碍的中药研究进展[J]. 中华男科学杂志, 2012, 18(3):260-265.
3. Zhu JF, Li ZJ, Zhang GS, et al. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3/AKT signalings[J]. PLoS One, 2011, 6(8):e23720.
4. Gazala S, Pelletier JS, Storie D, et al. A systematic review and meta-analysis to assess patient-reported outcomes after lung cancer surgery[J]. Sci World J, 2013, 2013:789625.
5. Chiba T, Yamada M, Aiso S. Targeting the JAK2/STAT3 axis in Alzheimer's disease[J]. Expert Opin Ther Targets, 2009, 13(10):1155-1167.
6. Kandala PK, Srivastava SK. DIMming ovarian cancer growth[J]. Curr Drug Targets, 2012, 13(14):1869-1875.
7. Sami A, Karsy M. Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma:novel therapeutic agents and advances in understanding[J]. Tumor Biol, 2013, 34(4):1991-2002.
8. Chen X, Ying Z, Lin X, et al. Acylglycerol kinase augments JAK2/STAT3 signaling in esophageal squamous cells[J]. J Clin Invest, 2013, 123(6):2576-2589.
9. He J, Wang Y, Duan F, et al. Icaritin induces apoptosis of HepG2 cells via the JNK1 signaling pathway Independent of the estrogen receptor[J]. Planta Med, 2010, 76(16):1834-1839.
10. Sun L, Chen W, Qu L, et al. Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P-glycoprotein expression[J]. Mol Med Rep, 2013, 8(6):1883-1887.
11. Hong J, Zhang Z, Lv W, et al. Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer cells[J]. PLoS One, 2013, 8(8):e71347.
12. Guo Y, Zhang X, Meng J, et al. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells[J]. Eur J Pharmacol, 2011, 658(2/3):114-122.
13. Ye HY, Lou YJ. Estrogenic effects of two derivatives of icaritin on human breast cancer MCF-7 cells[J]. Phytomedicine, 2005, 12(10):735-741.
14. Huang X, Zhu D, Lou Y. A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells[J]. Eur J Pharmacol, 2007, 564(1/2/3):26-36.
15. Sun F, Indran IR, Zhang ZW, et al. A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants[J]. Carcinogenesis, 2015, 36(7):757-768.
16. Zhu S, Wang Z, Li Z, et al. Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3[J]. Oncotarget, 2015, 6(12):10460-10472.
17. Li S, Priceman SJ, Xin H, et al. Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma[J]. PLoS One, 2013, 8(12):e81657.

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Effect of Icaritin on Proliferation and Apoptosis of NCI-H446 Cells

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