Tanshinone IIA suppresses gastric cancer cell proliferation and migration by downregulation of FOXM1

Yu,Jiao; Wang,Xiaoxia; Li,Yuhua; Tang,Bin

doi:10.3892/or.2017.5408

Tanshinone IIA suppresses gastric cancer cell proliferation and migration by downregulation of FOXM1

Authors:
- Jiao Yu
- Xiaoxia Wang
- Yuhua Li
- Bin Tang
View Affiliations

Affiliations: Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong 276000, P.R. China, Linyi Tumor Hospital, Linyi, Shandong 276000, P.R. China, Lanzhou Hengdao Chinese Medicine Institute, Lanzhou, Shandong 730000, P.R. China
Published online on: January 30, 2017 https://doi.org/10.3892/or.2017.5408
Pages: 1394-1400
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tanshinone IIA (TSN) exhibits a variety of anticancer effects. However, whether it inhibits gastric cancer (GC) cell proliferation and migration and the mechanism remain unclear. In the present study, different concentrations of TSN were co-incubated with SGC-7901 cells. The pcDNA-FOXM1 or FOXM1-siRNA plasmid was transfected into cells before treatment with 5 µg/l TSN. The proliferation and migration abilities of the SGC-7901 cells were tested by MTT and wound healing assays. Western blotting was used to investigate the expression levels of P21, Ki-67, PCNA, MMP-2, MMP-9 and FOXM1. We found that compared with the control, the proliferation and migration abilities of the SGC-7901 cells were decreased after incubation with different concentrations of TSN in a dose-dependent manner (p<0.01). Moreover, the expression levels of Ki-67, PCAN, MMP-2, MMP-9 and FOXM1 were decreased, and P21 was increased in the TSN-treated SGC-7901 cells (p<0.01). In addition, downregulation of FOXM1 by FOXM1-siRNA had the same effect as TSN on SGC-7901 cells, and overexpression of FOXM1 partly abrogated TSN-mediated inhibition of SGC-7901 cell proliferation and migration. These results suggested that TSN inhibits SGC-7901 cell proliferation and migration by downregulation of FOXM1.

View Figures

View References

1	Wang T, Chen T, Niu H, Li C, Xu C, Li Y, Huang R, Zhao J and Wu S: MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma cells by targeting BMI1. Int J Mol Med. 36:93–102. 2015.PubMed/NCBI
2	Xu S, Little PJ, Lan T, Huang Y, Le K, Wu X, Shen X, Huang H, Cai Y, Tang F, et al: Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in apolipoprotein-E knockout mice fed a high cholesterol diet. Arch Biochem Biophys. 515:72–79. 2011. View Article : Google Scholar : PubMed/NCBI
3	Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, et al: Sodium tanshinone IIA sulfonate inhibits canonical transient receptor potential expression in pulmonary arterial smooth muscle from pulmonary hypertensive rats. Am J Respir Cell Mol Biol. 48:125–134. 2013. View Article : Google Scholar : PubMed/NCBI
4	Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J and Wang W: Potential anticancer activity of tanshinone IIA against human breast cancer. Int J Cancer. 116:799–807. 2005. View Article : Google Scholar : PubMed/NCBI
5	Zhang HS, Zhang FJ, Li H, Liu Y, Du GY and Huang YH: Tanshinone IIA inhibits human esophageal cancer cell growth through miR-122-mediated PKM2 down-regulation. Arch Biochem Biophys. 598:50–56. 2016. View Article : Google Scholar : PubMed/NCBI
6	Qiu S, Granet R, Mbakidi JP, Brégier F, Pouget C, Micallef L, Sothea-Ouk T, Leger DY, Liagre B, Chaleix V, et al: Delivery of tanshinone IIA and α-mangostin from gold/PEI/cyclodextrin nanoparticle platform designed for prostate cancer chemotherapy. Bioorg Med Chem Lett. 26:2503–2506. 2016. View Article : Google Scholar : PubMed/NCBI
7	Lu M, Wang C and Wang J: Tanshinone I induces human colorectal cancer cell apoptosis: The potential roles of Aurora A-p53 and survivin-mediated signaling pathways. Int J Oncol. 49:603–610. 2016.PubMed/NCBI
8	Kim EO, Kang SE, Im CR, Lee JH, Ahn KS, Yang WM, Um JY, Lee SG and Yun M: Tanshinone IIA induces TRAIL sensitization of human lung cancer cells through selective ER stress induction. Int J Oncol. 48:2205–2212. 2016.PubMed/NCBI
9	Sanders DA, Ross-Innes CS, Beraldi D, Carroll JS and Balasubramanian S: Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells. Genome Biol. 14:R62013. View Article : Google Scholar : PubMed/NCBI
10	Ahmed M, Hussain AR, Siraj AK, Uddin S, Al-Sanea N, Al-Dayel F, Al-Assiri M, Beg S and Al-Kuraya KS: Co-targeting of Cyclooxygenase-2 and FoxM1 is a viable strategy in inducing anticancer effects in colorectal cancer cells. Mol Cancer. 14:1312015. View Article : Google Scholar : PubMed/NCBI
11	Zhang N, Xie Y, Li B, Ning Z, Wang A and Cui X: FoxM1 influences mouse hepatocellular carcinoma metastasis in vitro. Int J Clin Exp Pathol. 8:2771–2778. 2015.PubMed/NCBI
12	Zhang J, Zhang J, Cui X, Yang Y, Li M, Qu J, Li J and Wang J: FoxM1: A novel tumor biomarker of lung cancer. Int J Clin Exp Med. 8:3136–3140. 2015.PubMed/NCBI
13	Zhang Y, Li CF, Ma LJ, Ding M and Zhang B: MicroRNA-224 aggrevates tumor growth and progression by targeting mTOR in gastric cancer. Int J Oncol. 49:1068–1080. 2016.PubMed/NCBI
14	Kim HY, Cho Y, Kang H, Yim YS, Kim SJ, Song J and Chun KH: Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. Oncotarget. Jun 23–2016.(Epub ahead of print). doi: 10.18632/oncotarget.10231.
15	Kanda M, Shimizu D, Fujii T, Tanaka H, Tanaka Y, Ezaka K, Shibata M, Takami H, Hashimoto R, Sueoka S, et al: Neurotrophin receptor-interacting melanoma antigen-encoding gene homolog is associated with malignant phenotype of gastric cancer. Ann Surg Oncol. 23 Suppl 4:S532–S539. 2016. View Article : Google Scholar
16	Kanda M, Shimizu D, Fujii T, Tanaka H, Shibata M, Iwata N, Hayashi M, Kobayashi D, Tanaka C, Yamada S, et al: Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer. Int J Oncol. 49:1195–1202. 2016.PubMed/NCBI
17	Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, et al: MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 64:203–214. 2015. View Article : Google Scholar : PubMed/NCBI
18	Yu ZL, Wang JN, Wu XH, Xie HJ, Han Y, Guan YT, Qin Y and Jiang JM: Tanshinone IIA prevents rat basilar artery smooth muscle cells proliferation by inactivation of PDK1 during the development of hypertension. J Cardiovasc Pharmacol Ther. 20:563–571. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang C, Du X, Yang R, Liu J, Xu D, Shi J, Chen L, Shao R, Fan G, Gao X, et al: The prevention and treatment effects of tanshinone IIA on oestrogen/androgen-induced benign prostatic hyperplasia in rats. J Steroid Biochem Mol Biol. 145:28–37. 2015. View Article : Google Scholar : PubMed/NCBI
20	Tan X, Yang Y, Cheng J, Li P, Inoue I and Zeng X: Unique action of sodium tanshinone II-A sulfonate (DS-201) on the Ca2+ dependent BKCa activation in mouse cerebral arterial smooth muscle cells. Eur J Pharmacol. 656:27–32. 2011. View Article : Google Scholar : PubMed/NCBI
21	Yu Q, Sheng L, Yang M, Zhu M, Huang X and Li Q: Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule. PLoS One. 9:e1057562014. View Article : Google Scholar : PubMed/NCBI
22	Jing X, Xu Y, Cheng W, Guo S, Zou Y and He L: Tanshinone I induces apoptosis and pro-survival autophagy in gastric cancers. Cancer Chemother Pharmacol. 77:1171–1181. 2016. View Article : Google Scholar : PubMed/NCBI
23	Xu M, Cao FL, Li NY, Liu YQ, Li YP and Lv CL: Tanshinone IIA reverses the malignant phenotype of SGC7901 gastric cancer cells. Asian Pac J Cancer Prev. 14:173–177. 2013. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Li JX, Wang YQ and Miao ZH: Tanshinone I inhibits tumor angiogenesis by reducing Stat3 phosphorylation at Tyr705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells. Oncotarget. 6:16031–16042. 2015. View Article : Google Scholar : PubMed/NCBI
25	Lin JY, Ke YM, Lai JS and Ho TF: Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells. Phytomedicine. 22:929–938. 2015. View Article : Google Scholar : PubMed/NCBI
26	Wang CY, Hua L, Sun J, Yao KH, Chen JT, Zhang JJ and Hu JH: MiR-211 inhibits cell proliferation and invasion of gastric cancer by down-regulating SOX4. Int J Clin Exp Pathol. 8:14013–14020. 2015.PubMed/NCBI
27	Gormally MV, Dexheimer TS, Marsico G, Sanders DA, Lowe C, Matak-Vinković D, Michael S, Jadhav A, Rai G, Maloney DJ, et al: Suppression of the FOXM1 transcriptional programme via novel small molecule inhibition. Nat Commun. 5:51652014. View Article : Google Scholar : PubMed/NCBI
28	Song IS, Jeong YJ, Jeong SH, Heo HJ, Kim HK, Bae KB, Park YH, Kim SU, Kim JM, Kim N, et al: FOXM1-induced PRX3 regulates stemness and survival of colon cancer cells via maintenance of mitochondrial function. Gastroenterology. 149:1006–1016.e9. 2015. View Article : Google Scholar : PubMed/NCBI
29	Buchner M, Park E, Geng H, Klemm L, Flach J, Passegué E, Schjerven H, Melnick A, Paietta E, Kopanja D, et al: Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia. Nat Commun. 6:64712015. View Article : Google Scholar : PubMed/NCBI
30	Wiseman EF, Chen X, Han N, Webber A, Ji Z, Sharrocks AD and Ang YS: Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma. Mol Cancer. 14:692015. View Article : Google Scholar : PubMed/NCBI
31	Katoh M and Katoh M: Human FOX gene family (Review). Int J Oncol. 25:1495–1500. 2004.PubMed/NCBI
32	Hui MK, Chan KW, Luk JM, Lee NP, Chung Y, Cheung LC, Srivastava G, Tsao SW, Tang JC and Law S: Cytoplasmic Forkhead box M1 (FoxM1) in esophageal squamous cell carcinoma significantly correlates with pathological disease stage. World J Surg. 36:90–97. 2012. View Article : Google Scholar : PubMed/NCBI
33	Zhang Z, Zhang G and Kong C: FOXM1 participates in PLK1-regulated cell cycle progression in renal cell cancer cells. Oncol Lett. 11:2685–2691. 2016.PubMed/NCBI
34	Inoguchi S, Seki N, Chiyomaru T, Ishihara T, Matsushita R, Mataki H, Itesako T, Tatarano S, Yoshino H, Goto Y, et al: Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer. FEBS Lett. 588:3170–3179. 2014. View Article : Google Scholar : PubMed/NCBI