SLC39A1 contributes to gemcitabine resistance of pancreatic ductal adenocarcinoma by activating AMPK signaling
DOI:
https://doi.org/10.3329/bjp.v19i2.72787Keywords:
Adenocarcinoma, AMPK signaling, Gemcitabine, Pancreatic duct, SLC39A1, Western blotAbstract
Gemcitabine is a common first-line chemotherapy agent, but gemcitabine resistance is a clinical challenge for pancreatic ductal adenocarcinoma patients. Solute carrier 39A1 (SLCA39A1) as a zinc regulator presents a crucial function in the modulation of malignancy progression. Here, the impact of SLC39A1 on the gemcitabine resistance of pancreatic ductal adenocarcinoma was investigated. Immunohistochemistry demonstrated that the SLC39A1 expression was significantly up-regulated in gemcitabine-resistant pancreatic ductal adenocarcinoma samples compared with gemcitabine-sensitive ones. Gemcitabine dose-dependently inhibited the viability of the cancer cells, and SLC39A1 knockdown aggravated this effect. Both mRNA and protein expression of SLC39A1 were elevated in the gemcitabine-resistant cancer cells. SLC39A1 knockdown also reversed AMP-activated protein kinase (AMPK) phosphorylation and S6K expression of cancer cells regulated by the gemcitabine resistance. SLC39A1 promotes gemcitabine resistance of pancreatic ductal adenocarcinoma by activating AMPK signaling, revealing SLC39A1 may be a potential target in patients with gemcitabine resistance.
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Adachi, S, Yasuda I, Kawaguchi J, Yamauchi T, Nakashima M, Itani M, Nakamura M, Yoshioka T, Moriwaki H, Kozawa O. Ultraviolet enhances the sensitivity of pancreatic cancer cells to gemcitabine by activation of 5'-AMP-activated protein kinase. Biochem Biophys Res Commun. 2011; 414: 53-9.
Alluri, K, Nair KPM, Kotturu SK, Ghosh S. Transcriptional regulation of xinc transporters in human osteogenic sarcoma (Saos-2) cells to zinc supplementation and zinc depletion. Biol Trace Elem Res. 2020; 194: 360-67.
Binenbaum, Y, Na'ara S, Gil Z. Gemcitabine resistance in pan-creatic ductal adenocarcinoma. Drug Resist Updat. 2015; 23: 55-68.
Costello, LC, Franklin RB. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch Biochem Biophys. 2016; 611: 100-12.
Cui, XB, Shen YY, Jin TT, Li S, Li TT, Zhang SM, Peng H, Liu CX, Li SG, Yang L, Li N, Hu JM, Jiang JF, Li M, Liang WH, Li Y, Wei YT, Sun ZZ, Wu CY, Chen YZ, Li F. SLC39A6: A potential target for diagnosis and therapy of esophageal carcinoma. J Transl Med. 2015; 13: 321.
Ding, B, Lou W, Xu L, Li R, Fan W. Analysis the prognostic values of solute carrier (SLC) family 39 genes in gastric cancer. Am J Transl Res. 2019; 11: 486-98.
Han Y, Eom YS, Shah FH, Kim SJ. Destabilising microtubule polymerization regulates chondrocyte dedifferentiation and inflammation via nuclear factor kappa b and β-catenin pathway. Bangladesh J Pharmacol. 2023; 18: 8-16.
Hu, JX, Zhao CF, Chen WB, Liu QC, Li QW, Lin YY, Gao F. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol. 2021; 27: 4298-321.
Hu, ZI, O'Reilly EM. Therapeutic developments in pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024; 21: 7-24.
Ivey, GD, Shoucair S, Delitto DJ, Habib JR, Kinny-Koster B, Shubert CR, Lafaro KJ, Cameron JL, Burns WR, Burkhart RA, Thompson EL, Narang A, Zheng L, Wolfgang CL, He J. Postoperative chemotherapy is associated with improved survival in patients with node-positive pancreatic ductal adenocarcinoma after neoadjuvant therapy. World J Surg. 2022; 46: 2751-59.
Jia, Y, Gu D, Wan J, Yu B, Zhang X, Chiorean EG, Wang Y, Xie J. The role of GLI-SOX2 signaling axis for gemcitabine resistance in pancreatic cancer. Oncogene 2019; 38: 1764-77.
Jiang X, Xie J, Hu Z, Xiang X. Ethanol extract of Poria cocos induces apoptosis and differentiation in Neuro-2a neuroblastoma cells. Bangladesh J Pharmacol. 2022; 17: 105-113.
Li, XH, Huang GZ, Xu ZL, Zhao CY, Dong XY, Cui BK, Lin XJ. IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer. J Transl Med. 2023; 21: 911.
Lim HS, Jang Y, Moon BC, Park G. NF-κB signaling contributes to the inhibitory effects of Bombyx batryticatus on neuroinflammation caused by MPTP toxicity. Bangladesh J Pharmacol. 2021; 16: 96-102.
Ma, X, Zhuang H, Wang Q, Yang L, Xie Z, Zhang Z, Tan W, Tang C, Chen Y, Shang C. SLC39A1 overexpression is associated with immune infiltration in hepatocellular carcinoma and promotes its malignant progression. J Hepatocell Carcinoma. 2022; 9: 83-98.
Marin, RD, Crespo-Garcia S, Wilson AM, Sapieha P. RELi protocol: Optimization for protein extraction from white, brown and beige adipose tissues. MethodsX. 2019; 6: 918-28.
Nimmakayala, RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, Gupta R, Mallya K, Prajapati DR, Lele SM, T CC, J LG, Grandgenett PM, Hollingsworth MA, Murry DJ, Batra SK, Ponnusamy MP. Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene 2021; 40: 215-31.
Patzak, MS, Kari V, Patil S, Hamdan FH, Goetze RG, Brunner M, Gaedcke J, Kitz J, Jodrell DI, Richards FM, Pilarsky C, Gruetzmann R, Rümmele P, Knösel T, Hessmann E, Ellenrieder V, Johnsen SA, Neesse A. Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcita-bine resistance by reducing intracellular gemcitabine meta-bolites. EBioMedicine. 2019; 40: 394-405.
Qi, R, Bai Y, Li K, Liu N, Xu Y, Dal E, Wang Y, Lin R, Wang H, Liu Z, Li X, Wang X, Shi B. Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs. Drug Resist Updat. 2023; 68: 100960.
Sheng, N, Yan L, You W, Tan G, Gong J, Chen H, Yang Y, Hu L, Wang Z. Knockdown of SLC39A7 inhibits cell growth and induces apoptosis in human colorectal cancer cells. Acta Biochim Biophys Sin (Shanghai). 2017; 49: 926-34.
Sherman, MH, Beatty GL. Tumor microenvironment in pancreatic cancer pathogenesis and therapeutic resistance. Annu Rev Pathol. 2023; 18: 123-48.
Skrajnowska, D, Bobrowska-Korczak B. Role of zinc in immu-ne system and anti-cancer defense mechanisms. Nutrients 2019; 11.
Wang, M, Chen H, Wu Q, Huang Y, Zhou Y. Berberine triggers necroptosis of cervical H8 cells by activating receptor-interacting protein kinase 1. Bangladesh J Pharmacol. 2024; 19: 13-22.
Wang, P, Zhang J, He S, Xiao B, Peng X. SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas. Cancer Cell Int. 2020; 20: 573.
Wei, L, Wen JY, Chen J, Ma XK, Wu DH, Chen ZH, Huang JL. Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer. World J Gastroenterol. 2019; 25: 5590-603.
Xu, C, Wallace MB, Yang J, Jiang L, Zhai Q, Zhang Y, Hong C, Chen Y, Frank TS, Stauffer JA, Asbun HJ, Raimondo M, Woodward TA, Li Z, Guha S, Zheng L, Li M. ZIP4 is a novel diagnostic and prognostic marker in human pancreatic can-cer: A systemic comparison between EUS-FNA and surgical specimens. Curr Mol Med. 2014; 14: 309-15.
Xu, L, Ma X, Zhang X, Zhang C, Zhang Y, Gong S, Wu N, Zhang P, Feng X, Guo J, Zhao M, Ren Z, Zhang P. hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adeno-carcinoma. Mol Cancer. 2023; 22: 195.
Xu, XM, Wang CG, Zhu YD, Chen WH, Shao SL, Jiang FN, Liao QD. Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer. Onco Targets Ther. 2016; 9: 4197-205.
Yu, C, Chen S, Guo Y, Sun C. Oncogenic TRIM31 confers gem-citabine resistance in pancreatic cancer via activating the NF-κB signaling pathway. Theranostics 2018; 8: 3224-36.
Yu, D, Chen Y, Luo M, Peng Y, Yi S. Upregulated solute carrier SLC39A1 promotes gastric cancer proliferation and indicates unfavorable prognosis. Genet Res (Camb). 2022; 2022: 1256021.
Zhang, Q, Pan J, An F, Nie H, Zhan Q. Decreased SLC39A1 (solute carrier family 39 member 1) expression predicts unfa-vorable prognosis in patients with early-stage hepatocellular carcinoma. Bioengineered 2021; 12: 8147-56.
Zhou, B, Zhang SR, Chen G, Chen P. Developments and cha-llenges in neoadjuvant therapy for locally advanced pancreatic cancer. World J Gastroenterol. 2023; 29: 5094-103.
Zhou, L, Wang Q, Zhang H, Li Y, Xie S, Xu M. YAP inhibition by nuciferine via AMPK-mediated downregulation of HMGCR sensitizes pancreatic cancer cells to gemcitabine. Biomolecules 2019; 9.
Zhu, J, Chen Y, Ji Y, Yu Y, Jin Y, Zhang X, Zhou J. Gemcitabine induces apoptosis and autophagy via the AMPK/mTOR signaling pathway in pancreatic cancer cells. Biotechnol Appl Biochem. 2018; 65: 665-71.
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Copyright (c) 2024 Hao Yu, Xiaoping Mei, Xueming Zhang, Neng Qian, Qingjiang Yu, Hongkun Zhou
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