DOI QR코드

DOI QR Code

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

  • Song, Wei (Department of Oncology, Provincial Hospital Affiliated to Shandong University) ;
  • Jiang, Rui (Department of Oncology, Provincial Hospital Affiliated to Shandong University) ;
  • Zhao, Chun-Ming (Department of Opthalmology, Provincial Hospital Affiliated to Shandong University)
  • Published : 2012.11.30

Abstract

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

Keywords

References

  1. Berti C, Bartesaghi L, Ghidinelli M, et al (2011). Non-redundant function of dystroglycan and ${\beta}$1 integrins in radial sorting of axons. Development, 8, 4025-37.
  2. Brenner H, Rothenbacher D, Arndt V (2009). Epidemiology of stomach cancer. Cancer Epidemiology: Methods in Molecular Biology, 472, 467-77. https://doi.org/10.1007/978-1-60327-492-0_23
  3. Chen DQ, Yao DX, Zhao HY, et al (2012). DNA repair gene ERCC1 and XPD polymorphisms predict glioma susceptibility and prognosis. Asian Pac J Cancer Prev,6, 2791-4.
  4. Engelman JA (2009). Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer, 8, 550-62.
  5. Gao J, Zhu J, Li HY, et al (2011). Small interfering RNA targeting integrin-linked kinase inhibited the growth and induced apoptosis in human bladder cancer cells. Int J Biochem Cell Biol, 9, 1294-304.
  6. Karen-Ng LP, Marhazlinda J, Rahman ZA, et al (2011). Combined effects of isothiocyanate intake, glutathione S-transferase polymorphisms and risk habits for age of oral squamous cell carcinoma development. Asian Pac J Cancer Prev, 5, 1161-6.
  7. Keppler D (2011). Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol, 201, 299-323. https://doi.org/10.1007/978-3-642-14541-4_8
  8. Kim MK, Cho KJ, Kwon GY, et al (2008). ERCC1 predicting chemoradiation resistance and poor outcome in oesophageal cancer. Eur J Cancer, 1, 54-60.
  9. Martin LP, Hamilton TC, Schilder RJ (2008). Platinum resistance: the role of DNA repair pathways. Clin Cancer Res, 5, 1291-5.
  10. Li K, Lu Y, Liang J, et al (2009). RhoE enhances multidrug resistance of gastric cancer cells by suppressing Bax. Biochem Biophys Res Commun, 2, 212-6.
  11. Li W, Melton DW (2012). Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance. Oncogene, 19, 2412-22.
  12. Maeda O, Shibata K, Hosono S, et al (2012). Spectrin ${\alpha}$II and ${\beta}$II tetramers contribute to platinum anticancer drug resistance in ovarian serous adenocarcinoma. Int J Cancer, 1, 113-21.
  13. Pereira JA, Benninger Y, Baumann R, et al (2009). Integrinlinked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system. J Cell Biol, 1, 147-61.
  14. Piacentini P, Durante E, Trolese A, et al (2012).Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience. Gastric Cancer, 1, 106-10.
  15. Shah MA, Kelsen DP (2010). Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Canc Netw, 4, 437-47.
  16. Su JL, Chiou J, Tang CH, et al (2010). CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha} v{beta}3 integrin/integrin-linked kinase/ERK pathway. J Biol Chem, 41, 31325-36.
  17. Vilmar A, Sorensen JB (2009). Excision repair crosscomplementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer, 2, 131-9.
  18. Wagner EF, Nebreda AR (2009). Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer, 8, 537-49. https://doi.org/10.1038/nrd2932
  19. Wong RP, Ng P, Dedhar S, et al (2007). The role of integrinlinked kinase in melanoma cell migration, invasion, and tumor growth. Mol Cancer Ther, 6, 1692-700. https://doi.org/10.1158/1535-7163.MCT-07-0134
  20. Zhang Y, Qu X, Jing W, et al (2009).GSTP1 determines cisplatinum cytotoxicity in gastric adenocarcinoma MGC803 cells: regulation by promoter methylation and extracellular regulated kinase signaling. Anticancer Drugs, 3, 208-14.
  21. Zhao P, Dai M, Chen W, Li N (2010). Cancer trends in China. Jpn J Clin Oncol, 4, 281-5.

Cited by

  1. Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells vol.14, pp.11, 2013, https://doi.org/10.7314/APJCP.2013.14.11.6757
  2. Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6935
  3. Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells vol.15, pp.3, 2014, https://doi.org/10.7314/APJCP.2014.15.3.1403
  4. RNA silencing of integrin-linked kinase increases the sensitivity of the A549 lung cancer cell line to cisplatin and promotes its apoptosis vol.12, pp.1, 2015, https://doi.org/10.3892/mmr.2015.3471
  5. Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.875
  6. Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features vol.43, pp.3, 2016, https://doi.org/10.1002/biof.1344
  7. Glycosylation in Cancer: Interplay between Multidrug Resistance and Epithelial-to-Mesenchymal Transition? vol.6, pp.2234-943X, 2016, https://doi.org/10.3389/fonc.2016.00158
  8. Overexpression of ILK promotes temozolomide resistance in glioma cells vol.15, pp.3, 2017, https://doi.org/10.3892/mmr.2017.6157