Abstract：OBJECTIVE To investigate the effect of luteolin on the proliferation and metastasis of gastric cancer and its mechanism. METHODS BGC-823 and MGC-803 gastric cancer cells were cultured with RPMI 1640 medium containing 10% FBS. MTT assay was used to investigate the effect of different concentrations of luteolin (10, 20, 40 μmol·L-1) on the proliferation activity of gastric cancer cells. The effect of different concentrations of luteolin on the migration ability of gastric cancer cells was investigated by scratch experiment. Western blot was used to investigate the effect of luteolin on the expression of proliferation-related proteins, EMT-related proteins and HIF-1α. The effect of luteolin on HIF-1α mRNA expression was investigated by RT-PCR. siRNA knockdown of HIF-1α was used to investigate the effect of HIF-1α on the proliferation and migration of luteolin against gastric cancer cells. RESULTS The proliferation and migration of BGC-823 and MGC-803 gastric cancer cells were inhibited by luteolin in a concentration and time dependent manner. Luteolin inhibited the expression of p-AKT, p-mTOR, p-p70S6k, N-cadherin and vimentin and promoted E-cadherin expression. Luteolin inhibited the expression of HIF-1α in a dosage dependent manner at both mRNA and protein levels. HIF-1α knockdown weakened the ability of luteolin to resist the proliferation and migration of BGC-823 and MGC-803 gastric cancer cells. CONCLUSION Luteolin can inhibit the proliferation and metastasis of gastric cancer cells by inhibiting HIF-1α.
郭勇, 陈运芳, 王丽森, 邢海霞, 胡述博. 木犀草素通过HIF-1α抗胃癌细胞增殖和迁移的作用研究[J]. 中国药学杂志, 2021, 56(16): 1313-1319.
GUO Yong, CHEN Yun-fang, WANG Li-sen, XING Hai-xia, HU Shu-bo. Luteolin Inhibits the Proliferation and Migration of Gastric Cancer Via Inhibiting HIF-1α Expression . Chinese Pharmaceutical Journal, 2021, 56(16): 1313-1319.
LEE E J, OH S Y, SUNG M K. Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells [J]. Food Chem Toxicol, 2012, 50(11): 4136-4143.
[2]
YANG M Y, WANG C J, CHEN N F, et al. Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3 [J]. Chem Biol Interact, 2014, 213:60-68.
[3]
LIU Y, LANG T, JIN B, et al. Luteolin inhibits colorectal cancer cell epithelial-to-mesenchymal transition by suppressing CREB1 expression revealed by comparative proteomics study [J]. J Proteomics, 2017, 161:1-10.
[4]
FAN J J, HSU W H, LEE K H. Dietary flavonoids luteolin and quercetin inhibit migration and invasion of squamous carcinoma through reduction of Src/Stat3/S100A7 signaling [J]. Antioxidants, 2019, 8(11):557.
[5]
NAIKI-ITO A, NAIKI T, KATO H, et al. Recruitment of miR-8080 by luteolin inhibits androgen receptor splice variant 7 expression in castration-resistant prostate cancer [J]. Carcinogenesis, 2019, 41(8):1145-1157.
[6]
PARK S J, KIM H, KIM S H, et al. Epigenetic downregulation of STAT6 increases HIF-1alpha expression via mTOR/S6K/S6, leading to enhanced hypoxic viability of glioma cells [J]. Acta Neuropathol Commun, 2019, 7(1): 149.
[7]
DEBEN C, DESCHOOLMEESTER V, DE WAELE J. Hypoxia-induced cisplatin resistance in non-small cell lung cancer cells is mediated by HIF-1alpha and mutant p53 and can be overcome by induction of oxidative stress [J]. Cancers (Basel), 2018, 10(4):126.
[8]
SEMENZA G L. Targeting HIF-1 for cancer therapy [J]. Nat Rev Cancer, 2003, 3(10): 721-732.
[9]
LI C, WANG Q, SHEN S, et al. HIF-1alpha/VEGF signaling-mediated epithelial-mesenchymal transition and angiogenesis is critically involved in anti-metastasis effect of luteolin in melanoma cells [J]. Phytother Res, 2019, 33(3): 798-807.
[10]
GORDAN J D, LAL P, DONDETI V R, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma [J]. Cancer cell, 2008, 14(6): 435-446.
[11]
SU Q, FAN M, WANG J, et al. Sanguinarine inhibits epithelial-mesenchymal transition via targeting HIF-1alpha/TGF-beta feed-forward loop in hepatocellular carcinoma [J]. Cell Death Dis, 2019, 10(12): 939.
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