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藏红花素通过MTOR信号通路诱导卵巢癌HO-8910细胞自噬
Crocin Induced Autophagy through MTOR Signaling in Ovarian Cancer HO-8910 Cells

DOI: 10.12677/acm.2024.1492598, PP. 1297-1306

Keywords: 藏红花素,卵巢癌,HO-8910细胞,自噬,MTOR
Crocin
, Ovarian Cancer, HO-8910 Cell, Autophagy, MTOR

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Abstract:

目的:探讨藏红花素对卵巢癌HO-8910细胞自噬的影响及其分子机制。方法:用Western印迹法测定内源性LC3B-II蛋白的稳态水平以及MTOR及其下游底物的磷酸化水平。用荧光和共聚焦显微镜检测GFP-LC3B斑点的分布。结果:与对照细胞相比,用不同浓度的藏红花素处理的HO-8910细胞中内源性LC3B-II蛋白的稳态水平和GFP-LC3B斑点的分布以剂量依赖的方式增强。用藏红花素处理HO-8910细胞后,MTOR及其下游底物的磷酸化水平显著降低。结论:藏红花素通过抑制MTOR信号通路促进卵巢癌HO-8910细胞自噬体的形成。
Aims: To investigate the mechanism through which crocin influences the autophagy of ovarian cancer HO-8910 cells. Methods: Western blotting assay was used to determine the steady-state levels of endogenous LC3B-II protein and the phosphorylation level of MTOR and its downstream substrates. Fluorescence and confocal microscopy was used to detect the distribution of GFP-LC3B puncta. Results: Compared to the control cells, the steady-state levels of endogenous LC3B-II protein and the distribution of GFP-LC3B puncta were enhanced in the HO-8910 cells treated with various concentration of crocin in a dose-dependent manner. Following treatment of HO-8910 cells with crocin, the phosphorylation level of MTOR and its downstream substrates decreased significantly. Conclusions: Crocin promotes the formation of autophagosome in ovarian cancer HO-8910 cells by inhibiting the MTOR signaling pathway.

References

[1]  Yang, J., Wang, C., Zhang, Y., Cheng, S., Wu, M., Gu, S., et al. (2023) A Novel Autophagy-Related Gene Signature Associated with Prognosis and Immune Microenvironment in Ovarian Cancer. Journal of Ovarian Research, 16, Article No. 86.
https://doi.org/10.1186/s13048-023-01167-5
[2]  Jia, Y., Yang, H., Yu, J., Li, Z., Jia, G., Ding, B., et al. (2023) Crocin Suppresses Breast Cancer Cell Proliferation by Down‐Regulating Tumor Promoter miR‐122‐5p and up‐Regulating Tumor Suppressors FOXP2 and SPRY2. Environmental Toxicology, 38, 1597-1608.
https://doi.org/10.1002/tox.23789
[3]  Ghorbanzadeh, V., Hassan ALJAF, K.A., Wasman, H.M. and Dariushnejad, H. (2024) Crocin Inhibit the Metastasis of MDA-MB-231 Cell Line by Suppressing Epithelial to Mesenchymal Transition through Wnt/β-Catenin Signalling Pathway. Annals of Medicine & Surgery, 86, 1401-1407.
https://doi.org/10.1097/ms9.0000000000001691
[4]  Awad, B., Hamza, A.A., Al-Maktoum, A., Al-Salam, S. and Amin, A. (2023) Combining Crocin and Sorafenib Improves Their Tumor-Inhibiting Effects in a Rat Model of Diethylnitrosamine-Induced Cirrhotic-Hepatocellular Carcinoma. Cancers, 15, Article 4063.
https://doi.org/10.3390/cancers15164063
[5]  Abdu, S., Juaid, N., Amin, A., Moulay, M. and Miled, N. (2022) Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In vivo & in vitro Insights. Antioxidants, 11, Article 1645.
https://doi.org/10.3390/antiox11091645
[6]  Golestani, A., Rahimi, A., Najafzadeh, M., Sayadi, M. and Sajjadi, S.M. (2024) “Combination Treatments of Imatinib with Astaxanthin and Crocin Efficiently Ameliorate Antioxidant Status, Inflammation and Cell Death Progression in Imatinib-Resistant Chronic Myeloid Leukemia Cells”. Molecular Biology Reports, 51, Article No. 108.
https://doi.org/10.1007/s11033-023-09135-4
[7]  Li, Y., Guo, Q., Chen, R., Zhao, L., Cui, X., Deng, Y., et al. (2024) Crocin Combined with Cisplatin Regulates Proliferation, Apoptosis, and EMT of Gastric Cancer Cells via the FGFR3/MAPK/ERK Pathway in vitro and in vivo. Current Cancer Drug Targets, 24, 835-845.
https://doi.org/10.2174/1568009624666230915111239
[8]  Yang, H., Zhang, Y., Zhang, D., Qian, L., Yang, T. and Wu, X. (2023) Crocin Exerts Anti-Tumor Effect in Colon Cancer Cells via Repressing the JAK Pathway. European Journal of Histochemistry, 67, Article 3697.
https://doi.org/10.4081/ejh.2023.3697
[9]  Alyoussef, A. (2023) Investigation of the Ability of Crocin to Treat Skin Cancer Chemically Induced in Mice via the Inhibition of the Wnt/β-Catenin and Fibrotic Pathway. Cureus, 15, e38596.
https://doi.org/10.7759/cureus.38596
[10]  Bi, X., Jiang, Z., Luan, Z. and Qiu, D. (2021) Crocin Exerts Anti-Proliferative and Apoptotic Effects on Cutaneous Squamous Cell Carcinoma via miR-320a/ATG2B. Bioengineered, 12, 4569-4580.
https://doi.org/10.1080/21655979.2021.1955175
[11]  Niu, L., Wang, X.F. and Wang, X.R. (2020) Crocin Suppresses Cell Proliferation and Migration by Regulating miR-577/NFIB in Renal Cell Carcinoma. Journal of Biological Regulators and Homeostatic Agents, 34, 1523-1527.
[12]  Zhang, Y., Zhu, M., Krishna Mohan, S. and Hao, Z. (2020) Crocin Treatment Promotes the Oxidative Stress and Apoptosis in Human Thyroid Cancer Cells FTC‐133 through the Inhibition of STAT/JAK Signaling Pathway. Journal of Biochemical and Molecular Toxicology, 35, e22608.
https://doi.org/10.1002/jbt.22608
[13]  Zhang, J., Yang, S., Wang, K., Huang, Y., Yang, N., Yang, Z., et al. (2020) Crocin Induces Autophagic Cell Death and Inhibits Cell Invasion of Cervical Cancer SiHa Cells through Activation of PI3K/AKT. Annals of Translational Medicine, 8, Article 1180.
https://doi.org/10.21037/atm-20-5882
[14]  Bao, X., Hu, J., Zhao, Y., Jia, R., Zhang, H. and Xia, L. (2023) Advances on the Anti-Tumor Mechanisms of the Carotenoid Crocin. PeerJ, 11, e15535.
https://doi.org/10.7717/peerj.15535
[15]  Wang, C., Ma, Q., Kim, S., Wang, D.H., Shoyama, Y. and Yuan, C. (2022) Effects of Saffron and Its Active Constituent Crocin on Cancer Management: A Narrative Review. Longhua Chinese Medicine, 5, Article 35.
https://doi.org/10.21037/lcm-21-72
[16]  Li, X., He, S. and Ma, B. (2020) Autophagy and Autophagy-Related Proteins in Cancer. Molecular Cancer, 19, Article No. 12.
https://doi.org/10.1186/s12943-020-1138-4
[17]  Rakesh, R., PriyaDharshini, L.C., Sakthivel, K.M. and Rasmi, R.R. (2022) Role and Regulation of Autophagy in Cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1868, Article 166400.
https://doi.org/10.1016/j.bbadis.2022.166400
[18]  Jovanović, L., Nikolić, A., Dragičević, S., Jović, M. and Janković, R. (2022) Prognostic Relevance of Autophagy-Related Markers P62, LC3, and Beclin1 in Ovarian Cancer. Croatian Medical Journal, 63, 453-460.
https://doi.org/10.3325/cmj.2022.63.453
[19]  Nokhostin, F., Azadehrah, M. and Azadehrah, M. (2022) The Multifaced Role and Therapeutic Regulation of Autophagy in Ovarian Cancer. Clinical and Translational Oncology, 25, 1207-1217.
https://doi.org/10.1007/s12094-022-03045-w
[20]  Feng, C. and Yuan, X. (2023) Role of Autophagy and Its Regulation by Noncoding RNAs in Ovarian Cancer. Experimental Biology and Medicine, 248, 1001-1012.
https://doi.org/10.1177/15353702231151958
[21]  Mirabdali, S., Ghafouri, K., Farahmand, Y., Gholizadeh, N., Yazdani, O., Esbati, R., et al. (2024) The Role and Function of Autophagy through Signaling and Pathogenetic Pathways and LncRNAs in Ovarian Cancer. Pathology-Research and Practice, 253, Article 154899.
https://doi.org/10.1016/j.prp.2023.154899
[22]  Park, M., Choe, S., Shin, M., Kim, A., Mo, K., Kwon, H., et al. (2023) Potential Therapeutic Targets in Ovarian Cancer: Autophagy and Metabolism. Frontiers in Bioscience-Landmark, 28, Article 47.
https://doi.org/10.31083/j.fbl2803047
[23]  Xia, D. (2015) Ovarian Cancer HO-8910 Cell Apoptosis Induced by Crocin in Vitro. Natural Product Communications, 10.
https://doi.org/10.1177/1934578x1501000208
[24]  Debnath, J., Gammoh, N. and Ryan, K.M. (2023) Autophagy and Autophagy-Related Pathways in Cancer. Nature Reviews Molecular Cell Biology, 24, 560-575.
https://doi.org/10.1038/s41580-023-00585-z
[25]  Klionsky, D.J., Petroni, G., Amaravadi, R.K., Baehrecke, E.H., Ballabio, A., Boya, P., et al. (2021) Autophagy in Major Human Diseases. The EMBO Journal, 40, e108863.
https://doi.org/10.15252/embj.2021108863
[26]  Orfanelli, T., Jeong, J.M., Doulaveris, G., Holcomb, K. and Witkin, S.S. (2013) Involvement of Autophagy in Cervical, Endometrial and Ovarian Cancer. International Journal of Cancer, 135, 519-528.
https://doi.org/10.1002/ijc.28524
[27]  Wu, Q., Cui, Z., Jiang, S., Xia, H., Liu, L., You, Y., et al. (2023) Autophagy‐Related Gene PXN as a Prognostic Marker: Promotion of Ovarian Cancer Progression by Suppressing the P110β/Vps34/Beclin1 Pathway. Cell Biochemistry and Function, 41, 599-608.
https://doi.org/10.1002/cbf.3815
[28]  Bildik, G., Gray, J.P., Mao, W., Yang, H., Ozyurt, R., Orellana, V.R., et al. (2024) DIRAS3 Induces Autophagy and Enhances Sensitivity to Anti-Autophagic Therapy in KRAS-Driven Pancreatic and Ovarian Carcinomas. Autophagy, 20, 675-691.
https://doi.org/10.1080/15548627.2023.2299516
[29]  Xiong, Y., Liu, T. and Chen, J. (2023) Anisomycin Has the Potential to Induce Human Ovarian Cancer Stem Cell Ferroptosis by Influencing Glutathione Metabolism and Autophagy Signal Transduction Pathways. Journal of Cancer, 14, 1202-1215.
https://doi.org/10.7150/jca.83355
[30]  Jin, Y., Qiu, J., Lu, X. and Li, G. (2022) C-MYC Inhibited Ferroptosis and Promoted Immune Evasion in Ovarian Cancer Cells through NCOA4 Mediated Ferritin Autophagy. Cells, 11, Article 4127.
https://doi.org/10.3390/cells11244127
[31]  Meng, Y., Qiu, L., Zeng, X., Hu, X., Zhang, Y., Wan, X., et al. (2022) Targeting CRL4 Suppresses Chemoresistant Ovarian Cancer Growth by Inducing Mitophagy. Signal Transduction and Targeted Therapy, 7, Article No. 388.
https://doi.org/10.1038/s41392-022-01253-y
[32]  Shi, X., Yu, Q., Wang, K., Fu, Y., Zhang, S., Liao, Z., et al. (2023) Active Ingredients Isorhamnetin of Croci Srigma Inhibit Stomach Adenocarcinomas Progression by MAPK/mTOR Signaling Pathway. Scientific Reports, 13, Article No. 12607.
https://doi.org/10.1038/s41598-023-39627-z
[33]  Haseli, R., Honarvar, M., Yavari, K. and Ghavami, M. (2023) Synergistic Anticancer Effects of Crocin Combined with Deuterium-Depleted Water on HT-29 Cells. Anti-Cancer Drugs, 34, 1162-1170.
https://doi.org/10.1097/cad.0000000000001512
[34]  林珊, 屈思萌, 张荣, 等. 藏红花素诱导视网膜母细胞瘤自噬性死亡并抑制细胞侵袭和PI3K/AKT的活化[J]. 解剖学杂志, 2022, 45(6): 542-546.
[35]  Ebrahimi, N., Javadinia, S.A., Salek, R., Fanipakdel, A., Sepahi, S., Dehghani, M., et al. (2024) Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin during Chemoradiation for Esophageal Squamous Cell Carcinoma. Cancer Investigation, 42, 155-164.
https://doi.org/10.1080/07357907.2024.2319754
[36]  许存庚, 骆玉霜. 藏红花素联合顺铂通过抑制ERK信号通路调控胃癌细胞的增殖和凋亡[J]. 山西医科大学学报, 2019, 50(7): 922-927.
[37]  Kim, B. and Park, B. (2024) [Corrigendum] Saffron Carotenoids Inhibit STAT3 Activation and Promote Apoptotic Progression in Il-6-Stimulated Liver Cancer Cells. Oncology Reports, 51, Article No. 68.
https://doi.org/10.3892/or.2024.8727
[38]  Hosseini, S.S., Reihani, R.Z., Doustvandi, M.A., Amini, M., Zargari, F., Baradaran, B., et al. (2022) Synergistic Anticancer Effects of Curcumin and Crocin on Human Colorectal Cancer Cells. Molecular Biology Reports, 49, 8741-8752.
https://doi.org/10.1007/s11033-022-07719-0

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