DOI QR코드

DOI QR Code

Influence of the MACC1 Gene on Sensitivity to Chemotherapy in Human U251 Glioblastoma Cells

  • Shang, Chao (Department of Neurobiology, College of Basic Medicine, China Medical University) ;
  • Hong, Yang (Department of Neurosurgery, Shengjing Hospital, China Medical University) ;
  • Guo, Yan (Department of Central Laboratory, School of Stomatology, China Medical University) ;
  • Liu, Yun-Hui (Department of Neurosurgery, Shengjing Hospital, China Medical University) ;
  • Xue, Yi-Xue (Department of Neurobiology, College of Basic Medicine, China Medical University)
  • Published : 2015.02.04

Abstract

Background: This study was conducted to determine the influence of MACC1 expression on chemotherapy sensitivity in human U251 glioblastoma cells. Materials and Methods: Expression of the MACC1 gene in 49 cases of human brain glioma was determined by quantitative real-time PCR. Silencing effects of RNA interference on MACC1 was detected by Western-blotting. Flow cytometry methods and methyl thiazolyl tetrazolium assay (MTT) were used to determine the apoptosis and growth inhibitory rates of the U251 cells with MACC1 silencing. before and after treatment with cisplatin (DDP). Results: MACC1 mRNA in gliomas was up-regulated remarkably, to 158.8% of that in peri-cancerous tissues (P<0.05). The siRNA-MACC1 could inhibit the expression of MACC1 protein significantly (p<0.05), associated with an increase in apoptosis rate from 2.57% to 5.39% in U251 cells and elevation of the growth inhibitory rate from 1.5% to 17.8% (p<0.05 for both). After treatment with DDP at various concentrations (1, 3, $5{\mu}g/ml$), compared with control U251 cells, the apoptosis rate of MACC1-silenced U251 cells rose from 8.41%, 13.2% and 19.5% to 12.8%, 17.8% and 25.8%; the growth inhibitory rate increased from 16.2%, 19.3% and 24.5% to 23.7%, 28.4% and 36.3%. Conclusions: There is a notable relationship between over-expression of MACC1 and the characteristics of glioma cells. Silencing of MACC1 was found to enhance the apoptosis and growth inhibitory rates of U251 glioma cells, and thereby increase their sensitivity to DDP chemotherapy.

Keywords

Brain glioma;chemotherapy sensitivity;MACC1 gene;U251 cell

Acknowledgement

Supported by : National Nature Science Foundation of China

References

  1. Meng F, Li H, Shi H, et al (2013). MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/$\beta$-catenin signaling pathway. PLoS One, 4, 60821.
  2. Mrugala MM (2013). Advances and challenges in the treatment of glioblastoma: a clinician's perspective. Discov Med, 83, 221-30.
  3. Nieder C, Astner ST, Mehta MP, et al (2008). Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma. Am J Clin Oncol, 31, 300-5. https://doi.org/10.1097/COC.0b013e31815e3fdc
  4. Shang C, Zhang H, Guo Y, et al (2014). MiR-320a downregulation mediates bladder carcinoma invasion by targeting ITGB3. Mol Biol Rep, 4, 2521-7.
  5. Stein U, Walther W, Arlt F, et al (2009). MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med, 1, 59-67.
  6. Ugur HC, Taspinar M, Ilgaz S, et al (2014). Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide-lomeguatrib combination. Mol Biol Rep, 2, 697-703.
  7. Vlachostergios PJ, Voutsadakis IA, Papandreou CN (2013). Mechanisms of proteasome inhibitor-induced cytotoxicity in malignant glioma. Cell Biol Toxicol, 4, 199-211.
  8. Wang Y, Hong Q, Wang J, et al (2014). Downregulated expression of metastasis associated in colon cancer 1 (MACC1) reduces gallbladder cancer cell proliferation and invasion. Tumour Biol, 4, 3771-8.
  9. Wang Z, Li Z, Wu C, et al (2014). MACC1 overexpression predicts a poor prognosis for non-small cell lung cancer. Med Oncol, 1, 790.
  10. Yamamoto H, Miyoshi N, Mimori K, et al (2014). MACC1 expression levels as a novel prognostic marker for colorectal cancer. Oncol Lett, 5, 2305-9.
  11. Yang I, Aghi MK (2009). New advances that enable identification of glioblastoma recurrence. Nat Rev Clin Oncol, 6, 648-57. https://doi.org/10.1038/nrclinonc.2009.150
  12. Yang T, Kong B, Kuang YQ, et al (2014). Overexpression of MACC1 protein and its clinical implications in patients with glioma. Tumour Biol, 1, 815-9.
  13. Zhang K, Tian F, Zhang Y, et al (2014). MACC1 is involved in the regulation of proliferation, colony formation, invasion ability, cell cycle distribution, apoptosis and tumorigenicity by altering Akt signaling pathway in human osteosarcoma. Tumour Biol, 3, 2537-48.
  14. Zhen T, Dai S, Li H, et al (2014). MACC1 promotes carcinogenesis of colorectal cancer via β-catenin signaling pathway. Oncotarget, 11, 3756-69.
  15. Zhou YT, Li K, Tian H (2013). Effects of vinorelbine on cisplatin resistance reversal in human lung cancer A549/DDP cells. Asian Pac J Cancer Prev, 14, 4635-9. https://doi.org/10.7314/APJCP.2013.14.8.4635
  16. Burgio E, Migliore L (2014). Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics. Mol Biol Rep, [Epub ahead of print].
  17. Hagemann C, Fuchs S, Monoranu CM, et al (2013). Impact of MACC1 on human malignant glioma progression and patients' unfavorable prognosis. Neuro Oncol, 12, 1696-709.
  18. Jiang S, Yuan S, Wang Y, et al (2000). Study on sensitivity of neuroglioma to chemotherapeutic drugs. Hua Xi Yi Ke Da Xue Xue Bao, 31, 191-2.
  19. Kuhnt D, Becker A, Ganslandt O, et al (2011). Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol, 12, 1339-48.
  20. Ma J, Ma J, Meng Q, et al (2013). Prognostic value and clinical pathology of MACC-1 and c-MET expression in gastric carcinoma. Pathol Oncol Res, 4, 821-32.

Cited by

  1. Knockdown of MACC1 expression increases cisplatin sensitivity in cisplatin-resistant epithelial ovarian cancer cells vol.35, pp.4, 2016, https://doi.org/10.3892/or.2016.4585
  2. Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer vol.14, pp.4, 2017, https://doi.org/10.3892/ol.2017.6670
  3. Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway vol.14, pp.4, 2017, https://doi.org/10.3892/ol.2017.6790
  4. MACC1—the first decade of a key metastasis molecule from gene discovery to clinical translation vol.37, pp.4, 2018, https://doi.org/10.1007/s10555-018-9771-8