Suppression of SREBP-1 Expression by Simvastatin Decreases Visfatin-Induced Chemoresistance to Sunitinib in Human Renal Carcinoma 786-O Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Culture
2.3. MTT Assay
2.4. Real-Time Quantitative PCR
2.5. Western Blot Analysis
2.6. Dominant Negative (DN)-Akt and siRNA Transfection
2.7. ROS Measurement
2.8. Statistical Analysis
3. Results
3.1. Visfatin Increases the SREBP-1 Expression in 786-O Cells
3.2. SREBP-1 Expression Level Affects the Visfatin-Treated 786-O Cell Cytotoxicity of Sunitinib Treatment
3.3. Akt and p70S6K Signaling Regulates SREBP-1 Expression and Cell Cytotoxicity of 786-O Cells
3.4. ROS Regulates SREBP-1 Expression and Cell Cytotoxicity of 786-O Cells
3.5. Simvastatin Enhances Sunitinib-Induced Cell Cytotoxicity in Visfatin-Treated 786-O Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Linehan, W.M.; Ricketts, C.J. The Cancer Genome Atlas of renal cell carcinoma: Findings and clinical implications. Nat. Rev. Urol. 2019, 16, 539–552. [Google Scholar] [CrossRef] [PubMed]
- Xiao, Y.; Meierhofer, D. Glutathione Metabolism in Renal Cell Carcinoma Progression and Implications for Therapies. Int. J. Mol. Sci. 2019, 20, 3672. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strizova, Z.; Bartunkova, J.; Smrz, D. The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma. Cancer Immunol. Immunother. 2019, 68, 1831–1838. [Google Scholar] [CrossRef] [PubMed]
- Morais, C. Sunitinib resistance in renal cell carcinoma. J. Kidney Cancer VHL 2014, 1, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Sharma, R.; Kadife, E.; Myers, M.; Kannourakis, G.; Prithviraj, P.; Ahmed, N. Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma. J. Exp. Clin. Cancer Res. 2021, 40, 186. [Google Scholar]
- Zhang, H.P.; Zou, J.; Xu, Z.Q.; Ruan, J.; Yang, S.D.; Yin, Y.; Mu, H.J. Association of leptin, visfatin, apelin, resistin and adiponectin with clear cell renal cell carcinoma. Oncol. Lett. 2017, 13, 463–468. [Google Scholar] [CrossRef] [Green Version]
- Rajandram, R.; Perumal, K.; Yap, N.Y. Prognostic biomarkers in renal cell carcinoma: Is there a relationship with obesity? Transl. Androl. Urol. 2019, 8, S138–S146. [Google Scholar] [CrossRef]
- Avgerinos, K.I.; Spyrou, N.; Mantzoros, C.S.; Dalamaga, M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism 2019, 92, 121–135. [Google Scholar] [CrossRef]
- Morris, E.V.; Edwards, C.M. Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma. J. Cell. Physiol. 2018, 233, 9159–9166. [Google Scholar] [CrossRef]
- Guo, D.; Bell, E.H.; Mischel, P.; Chakravarti, A. Targeting SREBP-1-driven lipid metabolism to treat cancer. Curr. Pharm. Des. 2014, 20, 2619–2626. [Google Scholar] [CrossRef] [Green Version]
- Triki, M.; Rinaldi, G.; Planque, M.; Broekaert, D.; Winkelkotte, A.M.; Maier, C.R.; Janaki Raman, S.; Vandekeere, A.; Van Elsen, J.; Orth, M.F.; et al. mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis. Cell Rep. 2020, 31, 107806. [Google Scholar] [CrossRef] [PubMed]
- Bombelli, S.; Torsello, B.; De Marco, S.; Lucarelli, G.; Cifola, I.; Grasselli, C.; Strada, G.; Bovo, G.; Perego, R.A.; Bianchi, C. 36-kDa Annexin A3 Isoform Negatively Modulates Lipid Storage in Clear Cell Renal Cell Carcinoma Cells. Am. J. Pathol. 2020, 190, 2317–2326. [Google Scholar] [CrossRef] [PubMed]
- Sethi, G.; Shanmugam, M.K.; Kumar, A.P. SREBP-1c as a molecular bridge between lipogenesis and cell cycle progression of clear cell renal carcinoma. Biosci. Rep. 2017, 37, BSR20171270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barbalata, C.I.; Tefas, L.R.; Achim, M.; Tomuta, I.; Porfire, A.S. Statins in risk-reduction and treatment of cancer. World J. Clin. Oncol. 2020, 11, 573–588. [Google Scholar] [CrossRef] [PubMed]
- Jiang, W.; Hu, J.W.; He, X.R.; Jin, W.L.; He, X.Y. Statins: A repurposed drug to fight cancer. J. Exp. Clin. Cancer Res. 2021, 40, 241. [Google Scholar]
- Lee, K.C.; Wu, K.L.; Chang, S.F.; Chang, H.I.; Chen, C.N.; Chen, Y.Y. Fermented Ginger Extract in Natural Deep Eutectic Solvent Enhances Cytotoxicity by Inhibiting NF-κB Mediated CXC Chemokine Receptor 4 Expression in Oxaliplatin-Resistant Human Colorectal Cancer Cells. Antioxidants 2022, 11, 2057. [Google Scholar]
- Liu, J.L.; Huang, W.S.; Lee, K.C.; Tung, S.Y.; Chen, C.N.; Chang, S.F. Effect of 5-fluorouracil on excision repair cross-complementing 1 expression and consequent cytotoxicity regulation in human gastric cancer cells. J. Cell. Biochem. 2018, 119, 8472–8480. [Google Scholar] [CrossRef]
- Lee, K.C.; Wu, K.L.; Yen, C.K.; Chang, S.F.; Chen, C.N.; Lu, Y.C. Inhibition of NLRP3 by Fermented Quercetin Decreases Resistin-Induced Chemoresistance to 5-Fluorouracil in Human Colorectal Cancer Cells. Pharmaceuticals 2022, 15, 798. [Google Scholar]
- Chen, C.N.; Li, Y.S.; Yeh, Y.T.; Lee, P.L.; Usami, S.; Chien, S.; Chiu, J.J. Synergistic roles of platelet-derived growth factor-BB and interleukin-1β in phenotypic modulation of human aortic smooth muscle cells. Proc. Natl. Acad. Sci. USA 2006, 103, 2665–2670. [Google Scholar] [CrossRef] [Green Version]
- Chen, T.C.; Yen, C.K.; Lu, Y.C.; Shi, C.S.; Hsieh, R.Z.; Chang, S.F.; Chen, C.N. The antagonism of 6-shogaol in high-glucose-activated NLRP3 inflammasome and consequent calcification of human artery smooth muscle cells. Cell Biosci. 2020, 10, 5. [Google Scholar] [CrossRef] [Green Version]
- Kim, E.K.; Jang, M.; Song, M.J.; Kim, D.; Kim, Y.; Jang, H.H. Redox-Mediated Mechanism of Chemoresistance in Cancer Cells. Antioxidants 2019, 8, 471. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duarte, J.A.; de Barros, A.L.B.; Leite, E.A. The potential use of simvastatin for cancer treatment: A review. Biomed. Pharmacother. 2021, 141, 111858. [Google Scholar] [CrossRef] [PubMed]
- Trivanović, D.; Vignjević Petrinović, S.; Okić Djordjević, I.; Kukolj, T.; Bugarski, D.; Jauković, A. Adipogenesis in Different Body Depots and Tumor Development. Front. Cell Dev. Biol. 2020, 8, 571648. [Google Scholar] [CrossRef]
- Bertolio, R.; Napoletano, F.; Mano, M.; Maurer-Stroh, S.; Fantuz, M.; Zannini, A.; Bicciato, S.; Sorrentino, G.; Del Sal, G. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat. Commun. 2019, 10, 1326. [Google Scholar] [CrossRef] [PubMed]
- Sun, Y.; He, W.; Luo, M.; Zhou, Y.; Chang, G.; Ren, W.; Wu, K.; Li, X.; Shen, J.; Zhao, X.; et al. SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism. Tumour Biol. 2015, 36, 4133–4141. [Google Scholar]
- Yang, J.; Stack, M.S. Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women. Cancers 2020, 12, 3469. [Google Scholar] [CrossRef]
- Wu, G.; Wang, Q.; Xu, Y.; Li, J.; Zhang, H.; Qi, G.; Xia, Q. Targeting the transcription factor receptor LXR to treat clear cell renal cell carcinoma: Agonist or inverse agonist? Cell Death Dis. 2019, 10, 416. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Wang, H.; Zhao, Q.; Xia, Y.; Hu, X.; Guo, J. PD-L1 induces epithelial-to-mesenchymal transition via activating SREBP-1c in renal cell carcinoma. Med. Oncol. 2015, 32, 212. [Google Scholar] [CrossRef]
- Gao, Y.; Nan, X.; Shi, X.; Mu, X.; Liu, B.; Zhu, H.; Yao, B.; Liu, X.; Yang, T.; Hu, Y.; et al. SREBP1 promotes the invasion of colorectal cancer accompanied upregulation of MMP7 expression and NF-κB pathway activation. BMC Cancer 2019, 19, 685. [Google Scholar]
- Shimano, H.; Sato, R. SREBP-regulated lipid metabolism: Convergent physiology-divergent pathophysiology. Nat. Rev. Endocrinol. 2017, 13, 710–730. [Google Scholar] [CrossRef]
- Bao, J.; Zhu, L.; Zhu, Q.; Su, J.; Liu, M.; Huang, W. SREBP-1 is an independent prognostic marker and promotes invasion and migration in breast cancer. Oncol. Lett. 2016, 12, 2409–2416. [Google Scholar] [PubMed] [Green Version]
- Liu, R.; Chen, Y.; Liu, G.; Li, C.; Song, Y.; Cao, Z.; Li, W.; Hu, J.; Lu, C.; Liu, Y. PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers. Cell Death Dis. 2020, 11, 797. [Google Scholar] [CrossRef] [PubMed]
- Zhang, B.; Wu, J.; Guo, P.; Wang, Y.; Fang, Z.; Tian, J.; Yu, Y.; Teng, W.; Luo, Y.; Li, Y. Down-Regulation of SREBP via PI3K/AKT/mTOR Pathway Inhibits the Proliferation and Invasion of Non-Small-Cell Lung Cancer Cells. OncoTargets Ther. 2020, 13, 8951–8961. [Google Scholar] [CrossRef]
- Yi, J.; Zhu, J.; Wu, J.; Thompson, C.B.; Jiang, X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc. Natl. Acad. Sci. USA 2020, 117, 31189–31197. [Google Scholar] [CrossRef] [PubMed]
- Milkovic, L.; Cipak Gasparovic, A.; Cindric, M.; Mouthuy, P.-A.; Zarkovic, N. Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts. Cells 2019, 8, 793. [Google Scholar] [CrossRef] [Green Version]
- Bhardwaj, V.; He, J. Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer. Int. J. Mol. Sci. 2020, 21, 3412. [Google Scholar] [CrossRef]
- Longo, J.; van Leeuwen, J.E.; Elbaz, M.; Branchard, E.; Penn, L.Z. Statins as Anticancer Agents in the Era of Precision Medicine. Clin. Cancer Res. 2020, 26, 5791–5800. [Google Scholar]
- Wang, T.; Seah, S.; Loh, X.; Chan, C.W.; Hartman, M.; Goh, B.C.; Lee, S.C. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway. Oncotarget 2016, 7, 2532–2544. [Google Scholar] [CrossRef] [Green Version]
- Xue, L.; Qi, H.; Zhang, H.; Ding, L.; Huang, Q.; Zhao, D.; Wu, B.J.; Li, X. Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy. Front. Oncol. 2020, 10, 1510. [Google Scholar] [CrossRef]
- Ahmadi, Y.; Karimian, R.; Panahi, Y. Effects of statins on the chemoresistance-The antagonistic drug-drug interactions versus the anti-cancer effects. Biomed. Pharmacother. 2018, 108, 1856–1865. [Google Scholar] [CrossRef]
- Nguyen, P.A.; Chang, C.C.; Galvin, C.J.; Wang, Y.C.; An, S.Y.; Huang, C.W.; Wang, Y.H.; Hsu, M.H.; Li, Y.J.; Yang, H.C. Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan. Cancer Sci. 2020, 111, 2965–2973. [Google Scholar] [CrossRef] [PubMed]
- Di Bello, E.; Zwergel, C.; Mai, A.; Valente, S. The Innovative Potential of Statins in Cancer: New Targets for New Therapies. Front. Chem. 2020, 8, 516. [Google Scholar] [CrossRef] [PubMed]
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Chen, T.-C.; Huang, C.-W.; Lo, C.-Y.; Chen, C.-N.; Chang, S.-F.; Chen, Y.-Y. Suppression of SREBP-1 Expression by Simvastatin Decreases Visfatin-Induced Chemoresistance to Sunitinib in Human Renal Carcinoma 786-O Cells. Life 2022, 12, 1890. https://doi.org/10.3390/life12111890
Chen T-C, Huang C-W, Lo C-Y, Chen C-N, Chang S-F, Chen Y-Y. Suppression of SREBP-1 Expression by Simvastatin Decreases Visfatin-Induced Chemoresistance to Sunitinib in Human Renal Carcinoma 786-O Cells. Life. 2022; 12(11):1890. https://doi.org/10.3390/life12111890
Chicago/Turabian StyleChen, Te-Chuan, Chen-Wei Huang, Chih-Yu Lo, Cheng-Nan Chen, Shun-Fu Chang, and Yih-Yuan Chen. 2022. "Suppression of SREBP-1 Expression by Simvastatin Decreases Visfatin-Induced Chemoresistance to Sunitinib in Human Renal Carcinoma 786-O Cells" Life 12, no. 11: 1890. https://doi.org/10.3390/life12111890