Objective To investigate the effects and mechanisms of sennoside B on the growth, invasion of A549 cells and tumorigenesis of nude mice. Methods A549 non-small cell lung cancer cells were treated with sennoside B at doses of 0, 5, 10 and 20 μM respectively. The cells were divided into four groups randomly according to the dose and then the follow-up experiment was proceeded. Brdu staining was used to detect the cell proliferation of each group, and Hoechst staining was used to detect apoptosis. Cell migration was detected by scratch test. Cell invasion was detected by Transwell assay. Protein expression levels of Ki67, PCNA, cl-caspase-3, cl-caspase-9, VEGF, N-cadherin and E-cadherin, as well as phosphorylation of STAT3 and ERK1/2 were detected by western blotting. Tumor-bearing mice model was established and the weight of tumor was tested. The expression of Ki67 and VEGF were detected by immunohistochemistry. Results Compared with the Control group, the result showed that the Brdu positive cells number, the invasion cells number in each sennoside B dosage group were significantly reduced（P<0.05）, the apoptosis rate increased significantly（P<0.05）, the rate of cells scratches healing（P<0.05）, the protein levels of ki67, PCNA and VEGF, N-cadherin decreased obviously（P<0.05）, the protein levels of cl-caspase-3, cl-caspase-9, E-cadherin increased significantly（P<0.05）, phosphorylation levels of STAT3 and ERK1/2 were significantly reduced （P<0.05）, and the weight of tumor and the expression levels of Ki67 and VEGF were decreased in tumor-bearing mice model（P<0.05）. Conclusions Sennoside B inhibits the phosphorylation of STAT3 and ERK1/2 and the growth of A549 cells.
Key words
Non-small cell lung cancer /
Sennoside B; STAT3 /
ERK1/2
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[2] Saintigny P, Burger JA. Recent advances in non-small cell lung cancer biology and clinical management[J]. Discov Med, 2012, 13(71): 287-97.
[3] Hsu HS, Huang PI, Chang YL, et al. Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall celllung cancer-derived CD133-positive cells[J]. Cancer, 2011, 117(13): 2970-2985.
[4] Ishibashi K, Kumamoto K, Kuwabara K, et al. Usefulness of sennoside as an agent for mechanical bowel preparation prior to elective colon cancer surgery[J]. Asian J Surg, 2012, 35(2): 81-87.
[5] Tajima Y, Ishida H, Yamamoto A, et al. Comparison of the risk of surgical site infection and feasibility of surgery between sennoside versus polyethylene glycol as a mechanical bowel preparation of elective colon cancer surgery: a randomized controlled trial[J]. Surg Today, 2016, 46(6): 735-740.
[6] Xu W, Xu J, Wang T, et al. Ellagic acid and sennoside B inhibit osteosarcoma cell migration, invasion and growth by repressing the expression of c-Jun[J]. Oncol Lett, 2018, 16(1): 898-904.
[7] Chen YC, Chang CN, Hsu HC, et al. Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells[J]. Life Sci, 2009, 84(25-26): 915-922.
[8] Lin CC, Ng LT, Hsu FF, et al. Cytotoxic effects of coptis chinensis and epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth[J]. Clin Exp Pharmacol Physiol, 2004, 31(1-2): 65-69.
[9] Chen M, Wu J, Luo Q, et al. The anticancer properties of herba epimedii and its main bioactive componentsicariin andicariside II[J]. Nutrients, 2016, 8(9): E563.
[10]Jafari SM, Joshaghani HR, Panjehpour M, et al. A2B adenosine receptor agonist induces cell cycle arrest and apoptosis in breast cancer stem cells via ERK1/2 phosphorylation[J]. Cell Oncol (Dordr), 2018, 41(1): 61-72.
[11]Liu C, Ding L, Bai L, et al. Folate receptor alpha is associated with cervical carcinogenesis and regulates cervical cancer cells growth by activating ERK1/2/c-Fos/c-Jun[J]. Biochem Biophys Res Commun, 2017, 491(4): 1083-1091.
[12]Xiao Y, Jiang Y, Song H, et al. RNF7 knockdown inhibits prostate cancer tumorigenesis by inactivation of ERK1/2 pathway[J]. Sci Rep, 2017, 7(3): 43683
[13]Lu T, Dang S, Zhu R, et al. Adamts18 deficiency promotes colon carcinogenesis by enhancing β-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer[J]. Oncotarget, 2017, 8(12): 18979-18990.
（下转第672页）
（上接第667页）
[14]Mao M, Zhang T, Wang Z, et al. Glaucocalyxin A-induced oxidative stress inhibits the activation of STAT3 signaling pathway and suppresses osteosarcoma progression in vitro and in vivo[J]. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(6): 1214-1225.
[15] Kuang X, Xiong J, Wang W, et al. PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway[J]. Life Sci, 2019, 219(2): 248-256.
[16] Lee SY, Kim W, Lee YG, et al. Identification of sennoside A as a novel inhibitor of the slingshot (SSH) family proteins related to cancer metastasis[J]. Pharmacol Res, 2017, 119(5): 422-430.
[17]Seyed Jafari SM, Wiedmer C, Cazzaniga S, et al. Correlation of vascular endothelial growth factor subtypes and their receptors with melanoma progression: a next-generation tissue microarray (ngTMA) automated analysis[J]. PLoS One, 2018, 13(11): e0207019.
[18]Liu W, Xu J, Wang M, et al. Tumor-derived vascular endothelial growth factor (VEGF)-a facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway[J]. Int J Oncol, 2011, 39(5): 1213-1220.
[19] Agostino NM, Saraceni C, Kincaid H, et al. A prospective evaluation of the role of vascular endothelial growth factor (VEGF) and the immune system in stage III/IV melanoma[J]. Springerplus, 2015, 4(4): 186.
[20] Felcht M, Thomas M. Angiogenesis in malignant melanoma[J]. J Dtsch Dermatol Ges, 2015, 13(2): 125-136.
[21]Song J, Feng L, Zhong R, et al. Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway[J]. Mol Carcinog, 2017, 56(1): 36-48.
[22]Lu R, Zhang YG, Sun J. STAT3 activation in infection and infection-associated cancer[J]. Mol Cell Endocrinol, 2017, 451(8): 80-87.
