Effects of kaempferol on biological behaviors of Tca-83 cells via TGFBR1 signaling pathway

doi:10.19438/j.cjoms.2025.02.001

Abstract

Abstract: PURPOSE: To explore the effect of kaempferol on the malignant biological behavior of Tca-83 cells through TGFBR1 pathway. METHODS: Human tongue squamous cell line Tca-83 cells were treated with different concentrations of kaempferol solution (25, 50, 100 mmol/L) and normal saline, which were set as experimental group and blank control group, respectively. CCK-8 assay was used to assess the growth of Tca-83 cells. The apoptotic status and cycle distribution of these cells were analyzed by flow cytometry, the effect of kaempferol on the invasive and migration ability of Tca-83 cells was detected by Transwell assay. Real-time quantitative PCR was used to detect the changes of mRNA expression of Bcl-2, Bax, Caspase-3 and TGFBR1 signaling pathways associated with apoptosis. SPSS 22.0 software package was used for data analysis. RESULTS: With the increase of kaempferol concentration and the extension of treatment time, the proliferation inhibition effect of cells in the experimental group was gradually enhanced in concentration and time-dependent way. The proportion of cells arrested in G0/G1 and S phase showed significant difference between groups(P< 0.05), and the experimental group had higher apoptosis rate than that of the blank control group (P< 0.05). Compared with the blank control group, the experimental group had smaller number of invaded and migrated cells (P< 0.05), and the number was gradually decreased with the increase of kaempferol concentrations. The mRNA expression of Bax and Caspase-3 in the experimental group was significantly higher than that in the blank control group, and the Bcl-2 mRNA expression was significantly lower than that in the blank control group(P< 0.05). The mRNA expressions of TGFBR1 and Smad 2/3 in the experimental groups were significantly lower than those in the blank control group(P< 0.05), and were decreased with the increase of kaempferol concentration (P< 0.05). CONCLUSIONS: The biological effects of kaempferol on Tca-83 cells include inhibition of their proliferation and migration capacity and promoting apoptosis, which may be related to its inhibition of the activation of the TGFBR1 signaling pathway.

Key words: Kaempferol, Tongue squamous cell carcinoma, Tca-83 cell, TGFBR1 pathway, Proliferation, Apoptosis, Migration

CLC Number:

R739.8

ZHOU Ting-ting, LI Dong-ya, CHEN Wei-fang, WANG Sheng-ming, GE Dian-kui. Effects of kaempferol on biological behaviors of Tca-83 cells via TGFBR1 signaling pathway[J]. China Journal of Oral and Maxillofacial Surgery, 2025, 23(2): 105-109.

References

[1] Gelažius R, Gervickas A, Petronis Ž, et al.Epidemiology of primary oral cancer diagnostics among dentists and physicians in Lithuania[J]. Stomatologija, 2019, 21(3): 83-91.
[2] Periferakis A, Periferakis K, Badarau IA, et al.Kaempferol: antimicrobial properties, sources, clinical, and traditional applications[J]. Int J Mol Sci, 2022, 23(23): 15054.
[3] Wang R, Deng Z, Zhu Z, et al.Kaempferol promotes non-small cell lung cancer cell autophagy via restricting Met pathway[J]. Phytomedicine, 2023,121: 155090.
[4] Zonneville J, Safina A, Truskinovsky AM, et al.TGF-β signaling promotes tumor vasculature by enhancing the pericyte-endothelium association[J]. BMC Cancer, 2018, 18(1): 670-671.
[5] Yin H, Chen L, Piao S, et al.M6A RNA methylation-mediated RMRP stability renders proliferation and progression of non-small cell lung cancer through regulating TGFBR1/SMAD2/SMAD3 pathway[J]. Cell Death Differ, 2023, 30(3): 605-617.
[6] Sreekumar VN.Global scenario of research in oral cancer[J]. J Maxillofac Oral Surg, 2019, 18(3): 354-359.
[7] 单思, 严小军, 刘红宁. 中医药治疗恶性肿瘤的研究进展[J]. 中华中医药杂志, 2018, 33(10): 4539-4541.
Shan S, Yan XJ, Liu HN.Present approach in research on treatment of malignant tumor with traditional Chinese medicine[J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2018, 33(10): 4539-4541.
[8] Zhu Q, Han Y, He Y, et al.Kaempferol improves breast cancer-related depression through the COX-2/PGE2 pathway[J]. Front Biosci (Landmark Ed), 2023, 28(11): 311.
[9] Amjad E, Sokouti B, Asnaashari S.A systematic review of anti-cancer roles and mechanisms of kaempferol as a natural compound[J]. Cancer Cell Int, 2022, 22(1): 260.
[10] 谭蓓蓓, 郭婧澜, 刘倩, 等. 山柰酚对前列腺癌骨转移模型小鼠的作用及其机制研究[J].中国临床药理学杂志, 2020, 36(3): 293-296.
Tan BB, Guo JL, Liu Q, et al.Effect and mechanism of kaempferol on bone metastasis of prostate cancer in mice[J]. The Chinese Journal of Clinical Pharmacology, 2020,36(3): 293-296.
[11] D'Aguanno S, Brignone M, Scalera S, et al. Bcl-2 dependent modulation of Hippo pathway in cancer cells[J]. Cell Commun Signal, 2024, 22(1): 277-294.
[12] Eskandari E, Eaves CJ.Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis[J]. J Cell Biol, 2022, 221(6): e202201159.
[13] Jiang F, Yu Q, Chu Y, et al.MicroRNA-98-5p inhibits proliferation and metastasis in non-small cell lung cancer by targeting TGFBR1[J]. Int J Oncol, 2019, 54(1): 128-138.
[14] 李艳青, 郭婷婷, 曾毅,等. miR-490-3p通过靶向调控TGFBR1抑制非小细胞肺癌细胞的增殖和侵袭[J]. 生物技术通讯, 2019,30(3):315-320.
Li YQ, Guo TT, Zeng Y, et al.miR-490-3p inhibits the proliferation and invasion of nonsmall cell lung cancer cells by targeting TGFBR1[J]. Letters in Biotechnology, 2019,30(3):315-320.
[15] Boudreault J, Wang N, Ghozlan M, et al.Transforming growth factor-β/Smad signaling inhibits melanoma cancer stem cell self-renewal, tumor formation and metastasis[J]. Cancers (Basel), 2024,16(1): 224.