Inhibition of lupinol on the malignant progression of lung cancer A549 cells through regulating Notch signaling pathway

Published on Jul. 02, 2024Total Views: 94 times Total Downloads: 32 times Download Mobile

Author: YIN Bingyi ¹  LIN Hongsheng ¹ ZHANG Chuchu ²

Affiliation: 1. Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China 2. Institute of Traditional Chinese Medicine Information, China Academy of Chinese Medical Sciences, Beijing 100091, China

Keywords: Lupeol Notch signaling pathway Lung cancer cell Proliferation Apoptosis Migration Invasion

DOI: 10.12173/j.issn.1008-049X.202403208

Reference: YIN Bingyi, LIN Hongsheng, ZHANG Chuchu.Inhibition of lupinol on the malignant progression of lung cancer A549 cells through regulating Notch signaling pathway[J].Zhongguo Yaoshi Zazhi,2024, 24(6):961-968.DOI: 10.12173/j.issn.1008-049X.202403208.[Article in Chinese]  Copied

Abstract
Full-text
References

Abstract

Objective To explore the mechanism of lupinol on the proliferation, apoptosis, migration and invasion of lung cancer cells through regulating Notch signaling pathway.

Methods Lung cancer cells A549 were cultured in vitro, and the cells were treated with lupeol at concentrations of 0, 15, 30, and 60 mg/L, with 0 mg/L being the control group and the rese being the lupeol dosage groups, the cells were treated with lupinol at the concentration of 60 mg/L and Notch pathway inhibitor DAPT at the concentration of 10 μmol/ L, which was recorded as the lupeol+DAPT group. Cell proliferation changes were detected by MTT; cell apoptosis was detected by flow cytometry; cell migration and invasion were detected by Transwell; protein expression of PCNA, Bcl-2, N-cadherin, E-cadherin, Notch-1 and Hes- 1 were detected by Western blot.

Results 15, 30, 60 mg/L lupeol group can significantly inhibit the cell viability, the number of migration cells and invading cells of lung cancer cells, significantly increase the rate of cell apoptosis, and reduce PCNA, N-cadherin, Bcl-2, Hes-1 and Notch-1 expression, increase E-cadherin expression (P<0.05). Compared with the lupeol group, the lupeol+DAPT group significantly reduced cell viability, the number of migrating cells and invaded cells, increased apoptosis rate, decreased PCNA, Bcl-2, Hes-1, Notch-1 and N-cadherin protein expression, and increased E-cadherin protein expression (P<0.05).

Conclusion Lupinol may inhibit the invasion, migration and proliferation of lung cancer cells through Notch signaling pathway, and induce apoptosis.

Full-text

Please download the PDF version to read the full text: download

References

1.Chen P, Liu Y, Wen Y, et al. Non-small cell lung cancer in China[J]. Cancer Commun (Lond), 2022, 42(10): 937-970. DOI: 10.1002/cac2.12359.

2.徐转转, 涂超超, 龚章沁, 等. 重组人血管内皮抑制素不同给药方式治疗非小细胞肺癌恶性胸腔积液的有效性和安全性的网状Meta分析[J]. 中国药师, 2024, 27(4): 697-710. [Xu ZZ, Tu CC, Gong ZQ, et al. Network Meta-analysis of the efficacy and safety of different administration methods of recombinant human endostatin in the treatment of malignant pleural effusion of non-small cell lung cancer[J]. China Pharmacist, 2024, 27(4): 697-710.] DOI: 10.12173/j.issn.1008-049X.202311198.

3.乔文姝, 赵海田, 姚磊. 羽扇豆烷型五环三萜生物活性研究进展[J]. 食品科学, 2020, 41(13): 235-241. [Qiao WS, Zhao HT, Yao L. Advances in understanding the biological activity of lupinane-type pentacyclic triterpenoids[J]. Food Science, 2020, 41(13): 235-241. DOI: 10.7506/spkx1002-6630-20190715-194.

4.吴元元, 费素娟, 苗蓓, 等. 羽扇豆醇介导MDM2-p53通路对胃癌细胞生物学行为的影响[J]. 现代生物医学进展, 2021, 21(1): 46-49, 57. [Wu YY, Fei SJ, Miao B, et al. Lupeol-mediated MDM2-p53 pathway affects on the biological behavior of gastric cancer cells and related mechanisms[J]. Progress in Modern Biomedicine, 2021, 21(1): 46-49, 57.] DOI: 10.13241/j.cnki.pmb.2021.01.008.

5.黄昱刚, 谭伶娟, 陈广. 羽扇豆醇调控miR-100-5p对非小细胞肺癌NCI-H1299细胞生物学行为的影响[J]. 天津医药, 2023, 51(2): 118-123. [Huang YG, Tan LJ, Chen G. Effects of lupeol on the biological behavior of non-small cell lung cancer NCI-H1299 cells by regulating miR-100-5p[J]. Tianjin Medical Journal, 2023, 51(2): 118-123.] DOI: 10.11958/20220899.

6.吴振, 胡彦建, 尹琦, 等. Notch信号通路与肿瘤细胞凋亡的研究进展[J]. 现代肿瘤医学, 2021, 29(5): 901-906. [Wu Z, Hu YJ, Yin Q, et al. Advance of notch signaling pathway regulating cell apoptosis in malignant tumor[J]. Journal of Modern Oncology, 2021, 29(5): 901-906.] DOI: 10.3969/j.issn.1672-4992.2021.05.041.

7.Chen Y, Chen Y, Liu W. Chaperonin containing TCP1 subunit 6A may activate notch and wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma[J]. Cancer Biol Ther, 2024, 25(1): 2287122. DOI: 10.1080/15384047.2023.2287122.

8.Tang LX, Su SF, Wan Q, et al. Novel long non-coding RNA LBX2-AS1 indicates poor prognosis and promotes cell proliferation and metastasis through notch signaling in non-small cell lung cancer[J]. Eur Rev Med Pharmacol Sci, 2019, 23(17): 7419-7429. DOI: 10.26355/eurrev_201909_18851.

9.Liu K, Zhang X, Xie L, et al. Lupeol and its derivatives as anticancer and anti-inflammatory agents: molecular mechanisms and therapeutic efficacy[J]. Pharmacol Res, 2021, 164: 105373. DOI: 10.1016/j.phrs.2020.105373.

10.Zhang X, Gao Z, Chen K, et al. Lupeol inhibits the proliferation and migration of MDA-MB-231 breast cancer cells via a novel crosstalk mechanism between autophagy and the EMT[J]. Food Funct, 2022, 13(9): 4967-4976. DOI: 10.1039/d2fo00483f.

11.张昕. 羽扇豆醇通过促进自噬抑制三阴性乳腺癌的作用机制研究[D]. 广州: 广州中医药大学, 2023. DOI: 10.27044/d.cnki.ggzzu.2023.000003.

12.刘博佳, 宁青, 钟荣玲, 等. 羽扇豆醇对人肝癌细胞HepG2和SK-HEP-1侵袭、转移的影响及机制研究[J]. 中国中药杂志, 2020, 45(24): 6028-6035. [Liu BJ, Ning Q, Zhong RL, et al. Effect of lupeol on invasion and metastasis of human hepatoma HepG2 and SK-HEP-1 cells and its mechanism[J]. China Journal of Chinese Materia Medica, 2020, 45(24): 6028-6035.] DOI: 10.19540/j.cnki.cjcmm.20200901.403.

13.张小鹰, 何金花, 王浩, 等. 羽扇豆醇联合miR-145-5p对前列腺癌细胞增殖与凋亡的影响[J]. 中国病理生理杂志, 2020, 36(8): 1413-1421. [Zhang XY, He JH, Wang H, et al. Effects of lupeol and miR-145-5p on proliferation and apoptosis of prostate carcinoma cells[J]. Chinese Journal of Pathophysiology, 2020, 36(8): 1413-1421.] DOI: 10.3969/j.issn.1000-4718.2020.08.010.

14.Cai F, Guo S, Huang S, et al. Rubimaillin suppresses proliferation, migration and invasion of prostate cancer cells via the Notch-1/MMP signaling pathway[J]. Cell Mol Biol (Noisy-le-grand), 2020, 66(2): 130-134. DOI: 10.14715/cmb/2020.66.2.21.

15.Ding R, Li G, Yao Y, et al. Transgelin-2 interacts with CD44 to regulate notch1 signaling pathway and participates in colorectal cancer proliferation and migration[J]. J Physiol Biochem, 2022, 78(1): 99-108. DOI: 10.1007/s13105-021-00843-8.

16.Jiang J, Ren H, Xu Y, et al. TRIM67 promotes the proliferation, migration, and invasion of non-small-cell lung cancer by positively regulating the notch pathway[J]. J Cancer, 2020, 11(5): 1240-1249. DOI: 10.7150/jca.38286.

17.Guo Y, Chi X, Qu S, et al. E3 ubiquitin-protein ligase 2 inhibits cell proliferation, migration, and invasion of non-small cell lung cancer through ubiquitination of notch1[J]. Acta Histochem, 2022, 124(1): 151818. DOI: 10.1016/j.acthis.2021.151818.

18.张媛媛, 马静, 何会娜, 等. 非小细胞肺癌组织中Notch1、PTEN表达相关性及其与患者预后的关系[J]. 山东医药, 2022, 62(29): 58-61. DOI: 10.3969/j.issn.1002-266X.2022.29.014.

19.Hao Z, Xiaoyu Z, Enhui G, et al. Luteolin suppresses lung cancer progression through targeting the circ_0000190/miR-130a-3p/notch-1 signaling pathway[J]. Journal of Chemotherapy (Florence, Italy), 2023, 35(4): 330-342. DOI: 10.1080/1120009X.2022.2102303.