Effects of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and its action mechanism

LYU Mengying; LUO Zhaoyong; WANG Weimin; LIANG Qiaoling; WANG Yang; QIAN Yayun; LIU Yanqing

doi:10.7619/jcmp.20220335

Journal of Clinical Medicine in Practice > 2022 > 26(13): 60-67. > DOI: 10.7619/jcmp.20220335

LYU Mengying, LUO Zhaoyong, WANG Weimin, LIANG Qiaoling, WANG Yang, QIAN Yayun, LIU Yanqing. Effects of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and its action mechanism[J]. Journal of Clinical Medicine in Practice, 2022, 26(13): 60-67. DOI: 10.7619/jcmp.20220335

Citation:

PDF (4671 KB)

Effects of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and its action mechanism

LYU Mengying^{1, 2},
LUO Zhaoyong^{1, 2},
WANG Weimin^{1, 2},
LIANG Qiaoling^{1, 2},
WANG Yang^{1, 2},
QIAN Yayun^{1, 2},
LIU Yanqing^{1, 2, ,}

1.
Medical College of Yangzhou University, Institute of Translational Medicine, Yangzhou, Jiangsu, 225001
2.
The Key Laboratory of Syndrome Differentiation and Treatment of Toxic Pathogen-based Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, Jiangsu, 225001

More Information

Received Date: January 25, 2022
Available Online: July 01, 2022

Graphical Abstract

Abstract

Abstract

Objective
To investigate impacts of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and uncover the potential mechanism.
Methods
Cell viability of HCT116 and HT29 cells treated with pristimerin at various concentrations was measured by Methyl Thiazolyl Tetrazolium (MTT) assay at different time points. The proliferation of HCT116 cells and HT29 cells treated with pristimerin at various concentrations was detected by 5-acetyney-2'-deoxyuridine (EdU) assay. Transwell experiment was performed to observe the effects of different concentrations of pristimerin on migration of HCT116 cells and HT29 cells. The influence of pristimerin on cell cycle of HCT116 cells and HT29 cells was tested by flow cytometry. Western blot was used to determine its impact on cell cycle-related proteins including cyclin E1, CDK2, p53, p27 and p21 as well as PI3K/Akt/mTOR signaling pathways.
Results
MTT tests revealed that the viability of HCT116 and HT29 cells after 12, 24, 36, 48 and 60 h treated by different concentrations of pristimerin decreased significantly, and changed in a dose and time-dependent manner. EdU tests showed that the positive cell rates of HCT116 cells treated with 0.5, 1, 2 μmol/L pristimerin for 24 h were lower than those of the control group, the difference was statistically significant (P < 0.001). After treatment with 1, 2 and 4 μmol/L pristimerin for 24 h, the positive cell rates of HT29 cells were lower than those of the control group, the difference was statistically significant (P < 0.001). Transwell experiment results showed that the number of HCT116 cells penetrating the subventricular membrane decreased, and the cell migration rates were lower than that of control cells after treatment with 0.5, 1, 2 μmol/L pristimerin for 24 h (P < 0.001). Flow cytometry results showed that pristimerin could induce cell cycle arrest of HCT116 and HT29 cells at G₀/G₁ stages. Western blot results displayed that p53, p21 and p27 protein expression were up-regulated and the expression of cyclin E1, CDK2, p-PI3K, p-Akt, mTOR and p-mTOR was down-regulated in HCT116 and HT29 cells treated by pristimerin(P < 0.05, P < 0.01 or P < 0.001).
Conclusion
Pristimerin could exert the proliferation and migration of HCT116 and HT29 cells, induce arrest at G₀/G₁ stages, and the molecular mechanism may be related to PI3K/Akt/mTOR signaling pathway.
- pristimerin,
- colorectal cancer,
- proliferation,
- migration,
- cell cycle,
- signaling pathway

FullText(HTML)

References (27)

References

[1]	KISHORE C, BHADRA P. Current advancements and future perspectives of immunotherapy in colorectal cancer research[J]. Eur J Pharmacol, 2021, 893: 173819. doi: 10.1016/j.ejphar.2020.173819
[2]	PIAWAH S, VENOOK A P. Targeted therapy for colorectal cancer metastases: a review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer[J]. Cancer, 2019, 125(23): 4139-4147. doi: 10.1002/cncr.32163
[3]	林先勇, 张西志. 血管生成抑制剂恩度联合化疗治疗晚期结直肠癌的研究进展[J]. 实用临床医药杂志, 2018, 22(11): 128-132. doi: 10.7619/jcmp.201811038
[4]	JIANG Z Z, ZHAO Y, ZHAO Y, et al. Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells[J]. Food Chem Toxicol, 2021, 147: 111919. doi: 10.1016/j.fct.2020.111919
[5]	LI J J, YAN Y Y, SUN H M, et al. Anti-cancer effects of pristimerin and the mechanisms: a critical review[J]. Front Pharmacol, 2019, 10: 746. doi: 10.3389/fphar.2019.00746
[6]	ZHAO Q, CHENG X R, YU W, et al. Pristimerin induces apoptosis and tumor inhibition of oral squamous cell carcinoma through activating ROS-dependent ER stress/Noxa pathway[J]. Phytomedicine, 2021, 92: 153723. doi: 10.1016/j.phymed.2021.153723
[7]	ZHAO Q, BI Y, ZHONG J, et al. Pristimerin suppresses colorectal cancer through inhibiting inflammatory responses and Wnt/β-catenin signaling[J]. Toxicol Appl Pharmacol, 2020, 386: 114813. doi: 10.1016/j.taap.2019.114813
[8]	ZHAO Q, LIU Y X, ZHONG J, et al. Pristimerin induces apoptosis and autophagy via activation of ROS/ASK₁/JNK pathway in human breast cancer in vitro and in vivo[J]. Cell Death Discov, 2019, 5: 125. doi: 10.1038/s41420-019-0208-0
[9]	LI J J, GUO Q R, LEI X P, et al. Pristimerin induces apoptosis and inhibits proliferation, migration in H1299 lung cancer cells[J]. J Cancer, 2020, 11(21): 6348-6355. doi: 10.7150/jca.44431
[10]	LEE S O, KIM J S, LEE M S, et al. Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells[J]. BMC Cancer, 2016, 16: 701. doi: 10.1186/s12885-016-2730-2
[11]	WANG W M, LI D, XIANG L L, et al. TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9[J]. Cell Adh Migr, 2019, 13(1): 273-284.
[12]	CANTERO-CID R, MONTALBÁN-HERNÁNDEZ K M, GUEVARA J, et al. Intertwined leukocyte balances in tumours and peripheral blood as robust predictors of right and left colorectal cancer survival[J]. World J Gastrointest Oncol, 2022, 14(1): 295-318. doi: 10.4251/wjgo.v14.i1.295
[13]	陈志强, 蔡光先. 中西医结合内科学[M]. 2版. 北京: 中国中医药出版社, 2012: 123-130.
[14]	吴继萍, 冯妮, 李晓林, 等. 中医辨证论治结直肠癌术后的临床研究[J]. 光明中医, 2011, 26(9): 1816-1818. doi: 10.3969/j.issn.1003-8914.2011.09.039
[15]	钟俐强, 杨斯皓, 周珍, 等. 从中医方剂学角度谈癌性疼痛治疗的君臣佐使[J]. 四川中医, 2016, 34(3): 44-45. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY201603021.htm
[16]	LIM S, KALDIS P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation[J]. Dev Camb Engl, 2013, 140(15): 3079-3093.
[17]	XIE J, LUO F X, SHI C Y, et al. Moringa oleifera alkaloids inhibited PC3 cells growth and migration through the COX-2 mediated Wnt/β-catenin signaling pathway[J]. Front Pharmacol, 2020, 11: 523962.
[18]	XU Y, NASRI M, DANNENMANN B, et al. NAMPT/SIRT2-mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells[J]. Stem Cell Res Ther, 2021, 12(1): 112. doi: 10.1186/s13287-021-02144-9
[19]	STUBBS C K, BIANCUCCI M, VIDIMAR V, et al. RAS specific protease induces irreversible growth arrest via p27 in several KRAS mutant colorectal cancer cell lines[J]. Sci Rep, 2021, 11(1): 17925. doi: 10.1038/s41598-021-97422-0
[20]	COLEMAN N, MOYERS J T, HARBERY A, et al. Clinical development of AKT inhibitors and associated predictive biomarkers to guide patient treatment in cancer medicine[J]. Pharmacogenomics Pers Med, 2021, 14: 1517-1535.
[21]	NOOROLYAI S, SHAJARI N, BAGHBANI E, et al. The relation between PI3K/AKT signalling pathway and cancer[J]. Gene, 2019, 698: 120-128. doi: 10.1016/j.gene.2019.02.076
[22]	ALZAHRANI A S. PI3K/Akt/mTOR inhibitors in cancer: at the bench and bedside[J]. Semin Cancer Biol, 2019, 59: 125-132. doi: 10.1016/j.semcancer.2019.07.009
[23]	POLIVKA J, JANKU F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway[J]. Pharmacol Ther, 2014, 142(2): 164-175. doi: 10.1016/j.pharmthera.2013.12.004
[24]	DIN S, NISAR M, RAMZAN M, et al. Latcripin-7A from Lentinula edodes C induces apoptosis, autophagy, and cell cycle arrest at G1 phase in human gastric cancer cells via inhibiting PI3K/Akt/mTOR signaling[J]. Eur J Pharmacol, 2021, 907: 174305. doi: 10.1016/j.ejphar.2021.174305
[25]	CAO W, LIU X, ZHANG Y, et al. BEZ235 increases the sensitivity of hepatocellular carcinoma to sorafenib by inhibiting PI3K/AKT/mTOR and inducing autophagy[J]. Biomed Res Int, 2021, 2021: 5556306.
[26]	MORI Y, SHIRAI T, TERAUCHI R, et al. Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo[J]. Oncotargets Ther, 2017, 10: 5703-5710. doi: 10.2147/OTT.S150071
[27]	YAN F X, LIAO R F, SILVA M, et al. Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway[J]. J Cell Mol Med, 2020, 24(11): 6208-6219. doi: 10.1111/jcmm.15249

[1]	SHI Xiaoqing, LYU Qunli, XIAO Peihua, WU Jianzhong, HONG Pei. Application value of constructing a prediction model based on nutritional status combined with clinical data for infectious complications after radical gastrectomy for gastric cancer[J]. Journal of Clinical Medicine in Practice, 2025, 29(2): 63-68, 74. DOI: 10.7619/jcmp.20243772
[2]	CHENG Xuejiao, DONG Guannan, WANG Kai, ZHANG Yucui, ZHAO Haijing, LI Yao, ZHANG Xiaowei. Relationships of nutritional status and length of stay with phase angle in patients with severe craniocerebral injury[J]. Journal of Clinical Medicine in Practice, 2024, 28(2): 105-108. DOI: 10.7619/jcmp.20233052
[3]	ZHANG Zhijian, CHEN Hanzhi, LI Cheng, ZHOU Leting, LIU Xiaobin, SHAN Weiwei, LIU Bin, WANG Liang. Evaluation method for anemia and nutritional status in hemodialysis patients based on bioelectrical impedance vector analysis[J]. Journal of Clinical Medicine in Practice, 2023, 27(15): 50-55. DOI: 10.7619/jcmp.20231283
[4]	ZHAO Dan, GUO Liang, DENG Yunqun, YANG Mingli, LI Lijie. Comparison in effect of two nutritional status scores in evaluating prognosis of high-grade T1 stage bladder cancer[J]. Journal of Clinical Medicine in Practice, 2021, 25(2): 93-96, 100. DOI: 10.7619/jcmp.20200580
[5]	SUN Xinjian, LI Wenjun, MA Haiyang, YE Linfeng, YANG Jing. Effect of sequential enteral nutrition versus parenteral nutrition in improving nutrional status for patients with severe cerebral hemorrhage[J]. Journal of Clinical Medicine in Practice, 2020, 24(6): 126-129. DOI: 10.7619/jcmp.202006035
[6]	XUE Lijuan, DENG Weiping, LU Weijun, SHANGGUAN Tao, HUA Yaowei. Effect of early enteral nutrition after total gastrectomy on nutritional status and hospitalized recovery of elderly patients with gastric cancer[J]. Journal of Clinical Medicine in Practice, 2020, 24(4): 97-100. DOI: 10.7619/jcmp.202004025
[7]	ZHANG Riguang, YANG Liu, CHEN Shaojun. Correlation between nutritional status of patients with adjuvant chemoradiotherapy after gastric cancer surgery and side effects[J]. Journal of Clinical Medicine in Practice, 2020, 24(2): 52-54. DOI: 10.7619/jcmp.202002015
[8]	XUE Hua, WEI Shengquan, WANG Zhijie, ZHAI Mei, WANG Xiaowei, DING Junbing, LIANG Jie, KANG Kai. Analysis of pulmonary function, nutritional status and oxidative stress ability in patients with chronic obstructive pulmonary disease in stable stage[J]. Journal of Clinical Medicine in Practice, 2019, 23(9): 65-68. DOI: 10.7619/jcmp.201909019
[9]	LIU Yue, ZUO Na. Effect of hemodiafiltration on micro-inflammation and nutritional status in maintenance hemodialysis patients[J]. Journal of Clinical Medicine in Practice, 2017, (4): 67-70. DOI: 10.7619/jcmp.201704021
[10]	LU Jian, GONG Lei, YANG Yisha, SUN Hui, NI Jingbin. Influence of enteral nutrition support combined with glutamine on liver function, nutritional status and intestinal barrier function of patients with decompensated cirrhosis[J]. Journal of Clinical Medicine in Practice, 2015, (1): 32-35. DOI: 10.7619/jcmp.201501010

Cited By

Get Citation

PDF

XML

Article views (219) PDF downloads (25)

Turn off MathJax

Article Contents

Abstract

References

Effects of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and its action mechanism

Abstract

References

Related Articles

Catalog

Effects of pristimerin on proliferation, migration and cell cycle of colorectal cancer HCT116 and HT29 cells and its action mechanism

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content