Effect of betulinic acid on proliferation of human gastric cancer SGC-7901 cells

doi:10.12047/j.cjap.6036.2020.131

Abstract

Abstract: Objective: Human gastric cancer SGC-7901 cells were treated with betulinic acid(BA)at the concentrations of 0, 10, 20, and 30 μg/ml, and treated with conventional chemotherapeutic drug 5-Fu as a positive control to explore its effect on cell proliferation. Trypan blue and GIEMSA staining method were used to investigate the effect of BA on cell growth inhibition and clone formation. EdU method and flow cytometry were used to explore the proliferation and cell cycle of SGC-7901 cells after treated with BA, respectively. qRT-PCR and Western blot were also applied to determine the mRNA and protein levels of cyclin D1 and cyclin B1. Results: The cell growth inhibition rate was increased after treated with different concentrations of BA in SGC-7901 cells(P＜0.05). After treated for 48 h, BA decreased the clone information and cell proliferation of SGC-7901 cells markedly in dose-and time-dependent manners (P＜0.01). Flow cytometry analysis showed that BA obviously increased the proportion of SGC-7901 cells in G1 phase but decreased the proportion of those in S phase. qRT-PCR and Western blot analysis showed that the mRNA and protein levels of cyclin D1 and cyclin B1 were significantly downregulated by BA at different concentrations(P＜0.01). Compared with the 5-Fu control group, when the concentration of BA was 20 μg/ml and 30 μg/ml, the cell proliferation ability was significantly decreased, the cell cycle was inhibited, and the expression of cyclin was reduced (all P＜0.05). Conclusion: The betulinic acid regulates the proliferation of SGC-7901 cells by inhibiting the expressions of cyclin D1 and cyclin B1, which leads to cell cycle arrest and proliferative inhibition.

Key words: betulinic acid, SGC-7901 cells, cell proliferation, cell cycle

CLC Number:

Q291

CHEN Ya-nan, SHAO Shu-li, HE Meng-qi, HUANG Xin, ZHANG Wei-wei, ZHANG Zhen-zhu. Effect of betulinic acid on proliferation of human gastric cancer SGC-7901 cells[J]. CJAP, 2020, 36(6): 628-632.

References

[1] Wang SC, Liu YW, Feng YB, et al. A review on curability of cancers: More efforts for novel therapeutic options are needed[J]. Cancers, 2019, 11(11): 1782.
[2] 方玫玫, 杨钰贤, 李舟, 等. 晚期胃癌不同一线化疗方案治疗及生存分析[J]. 转化医学杂志, 2019, 8(2): 89-94.
[3] Ankit S, Divya A, Robin K, et al. Therapeutic applications of betulinic acid nanoformulations[J]. Ann N Y Acad Sci, 2018, 1421(1): 5-18.
[4] Bildziukevich U, Ozdemir Z, Wimmer Z. Recent achievements in medicinal and supramolecular chemistry of betulinic acid and its derivatives[J]. Molecules, 2019, 24(19): 3546.
[5] Zhan XK, Li JL, Zhang S, et al. Betulinic acid exerts potent antitumor effects on paclitaxel-resistant human lung carcinoma cells (H460) via G2/M phase cell cycle arrest and induction of mitochondrial apoptosis[J]. Oncol Lett , 2018, 16(3): 3628-3634.
[6] Sun LK, Cao JY, Chen K, et al. Betulinic acid inhibits stemness and EMT of pancreatic cancer cells via activation of AMPK signaling[J]. Int J Oncol, 2019, 54(1): 98-110.
[7] 祝志鹏, 徐波, 张丽君, 等. 氟尿嘧啶联合TNF-α对人胃癌细胞SGC-7901的抑制作用[J]. 青岛大学学报(医学版), 2018, 54(6): 635-642.
[8] Chen ZY, Chen X, Chen P, et al. Long non-coding RNA SNHG20 promotes non-small cell lung cancer cell proliferation and migration by epigenetically silencing of P21 expression[J]. Cell Death Dis, 2017, 8(10): e3092-e3092.
[9] Huang X, Zang YL, Zhang MH, et al. Nuclear factor of κB1 is a key regulator for the transcriptional activation of milk synthesis in bovine mammary epithelial cells[J]. DNA Cell Biol, 2017, 36(4): 295-302.
[10] Wang QQ, Liu G L, Hu CH. Molecular classification of gastric adenocarcinoma[J]. Gastroenterology Res, 2019, 12(6): 275-282.
[11] 杨丹, 颜琼, 罗德兰, 等. 大蒜素对5-氟尿嘧啶治疗肝癌的增效作用及机制[J]. 中国中西医结合杂志, 2019, 39(1): 72-75.
[12] 王根桃, 黄松. 黄芩素对人口腔鳞癌细胞增殖和侵袭的作用及其机制[J]. 中国应用生理学杂志, 2018, 34(6): 536-540.
[13] 王瑜, 柯瑞君, 蒋盼若, 等. 杨芽黄素对前列腺癌细胞凋亡的影响及其机制[J]. 中国应用生理学杂志, 2019, 35(3): 283-288.
[14] Lee D, Lee SR, Kang KS, et al. Betulinic acid suppresses ovarian cancer cell proliferation through induction of apoptosis[J]. Biomolecules, 2019, 9(7): 257.
[15] Cai YL, Zheng YF, Gu JY, et al. Betulinic acid chemosensitizes breast cancer by triggering ER stress-mediated apoptosis by directly targeting GRP78[J]. Cell Death Dis, 2018, 9(6): 636.
[16] Xu T, Pang QY, Wang Y, et al. Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cells[J]. Int J Mol Med, 2017, 40(6): 1669-1678.
[17] Ingham M, Schwartz GK. Cell-cycle therapeutics come of age[J]. J Clin Oncol, 2017, 35(25): 2949-2959.
[18] Zhang T, Zhou Y, Li L, et al. CenpH regulates meiotic G2/M transition by modulating the APC/CCdh1-cyclin B1 pathway in oocytes[J]. Development, 2017, 144(2): 305-312.
[19] Ramos-Garcia P, Gil-Montoya JA, Scully C, et al. An update on the implications of cyclin D1 in oral carcinogenesis[J]. Oral Dis, 2017, 23(7): 897-912.