[an error occurred while processing this directive] | [an error occurred while processing this directive]
Silencing ANO9 increases the radiosensitivity of pancreatic cancer cell AsPC-1
Zhao Dongmei1, Ma Yanying1, Wang Wen2, Li xu1
1.Department of Pathology,Henan Cancer Hospital,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;2.Department of Radiation Oncology,Henan Cancer Hospital,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China
AbstractObjective To evaluate the effect of ANO9 on the radiosensitivity of pancreatic cancer cell AsPC-1, aiming to provide new targets for clinical radiotherapy of pancreatic cancer. Methods Western blot was performed to detect the expression of ANO9 in pancreatic cancer cell lines (BxPC-3, PANC-1, AsPC-1) and normal pancreatic cell line (HPNE). The AsPC-1 cell line with stable silencing ANO9 was constructed by using lentivirus and validated by Western blot. MTT assay was adopted to detect the cell viability of AsPC-1 with stable silencing ANO9 after irradiation. Colony formation assay was conducted to evaluate the effect of silencing ANO9 upon the radiosensitivity of AsPC-1 cells. Western blot was performed to assess the effect of ANO9 silencing on the expression of EGFR/ERK signaling protein. Results The expression levels of ANO9 were significantly up-regulated in three pancreatic cancer cell lines compared with that in the normal pancreatic cell line HPNE (t=7.426, 5.543, 11.850, all P<0.05). After silencing ANO9, the expression level of ANO9 protein was significantly down-regulated than that in the control group (t= 9.670, P<0. 05). The AsPC-1 cells with stable silencing ANO9 were successfully constructed. The sensitivity of AsPC-1 cells to irradiation was significantly increased after silencing ANO9, and the sensitivity enhancement ratio was 1.566. The expression levels of EGFR/ERK signaling proteins (EGFR and p-ERK1/2) were significantly down-regulated after silencing ANO9(t=7.949, 13.160, both P<0.05).Conclusions Silencing ANO9 can significantly increase the sensitivity of AsPC-1 cells to radiotherapy, which is probably associated with the inhibition of EGFR/ERK signaling transduction. ANO9 might be a new therapeutic target for preventing the progression of pancreatic cancer.
Zhao Dongmei,Ma Yanying,Wang Wen et al. Silencing ANO9 increases the radiosensitivity of pancreatic cancer cell AsPC-1[J]. Chinese Journal of Radiation Oncology, 2019, 28(5): 382-384.
Zhao Dongmei,Ma Yanying,Wang Wen et al. Silencing ANO9 increases the radiosensitivity of pancreatic cancer cell AsPC-1[J]. Chinese Journal of Radiation Oncology, 2019, 28(5): 382-384.
[1] Pedemonte N,Galietta LJ.Structure and function of TMEM16 proteins (anoctamins)[J].Phys Rev,2014,94(2):419-459.DOI:10.1152/physrev.00039.2011. [2]Picollo A,Malvezzi M,Accardi A.TMEM16 proteins:unknown structure and confusing functions[J].J Mol Biol,2015,427(1):94-105.DOI:10.1016/j.jmb.2014.09.028. [3]Katoh M,Katoh M.Identification and characterization of human TP53I5 and mouse Tp53i5 genes in silico[J].Int J Oncol,2004,25(1):225-230.DOI:10.1016/S0016-5085(13)60202-4. [4]Jun I,Park HS,Piao H,et al. ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer[J].Br J Cancer,2017,117(12):1798-1809.DOI:10.1038/bjc.2017.355. [5]Chen W,Zheng R,Baade PD,et al. Cancer statistics in China,2015[J].Ca A Cancer J Clinicians,2016,66(2):115-132.DOI:10.3322/caac.21338. [6]Miller KD,Siegel RL,Lin CC,et al. Cancer treatment and survivorship statistics,2016[J].Ca A Cancer J Clinicians,2016,66(4):271-289.DOI:10.3322/caac.21349. [7]Midha S,Chawla S,Garg PK.Modifiable and non-modifiable risk factors for pancreatic cancer:a review[J].Cancer Lett,2016,381(1):269-277.DOI:10.1016/j.canlet.2016.07.022. [8]Kinesh C,Rashmee P,Sushil D,et al. Endoscopic ultrasound-guided radiofrequency ablation of the pancreatic tumors:a promising tool in management of pancreatic tumors[J].Canadian J Gastroenterol Hepatol,2016,2016(2016):4189358.DOI:10.1155/2016/4189358. [9]Polireddy K,Chen Q.Cancer of the pancreas:molecular pathways and current advancement in treatment[J].J Cancer,2016,7(11):1497-1514.DOI:10.7150/jca.14922. [10]Hajj C,Goodman KA.Pancreatic cancer and SBRT:a new potential option?[J].Radiat Oncol,2015,20(5):377-384.DOI:10.1016/j.rpor.2015.05.008. [11]Goodman KA.Stereotactic body radiation therapy for pancreatic cancer[J].Cancer J,2016,22(4):290-295.DOI:10.1097/PPO.0000000000000206. [12]Hoffe S,Rao N,Shridhar R.Neoadjuvant vs. adjuvant therapy for resectable pancreatic cancer:the evolving role of radiation[J].Sem Radiat Oncol,2014,24(2):113-125.DOI:10.1016/j.semradonc.2013.11.002. [13]Xue J, Zhu W, Song J, et al. Activation of PPARα by clofibrate sensitizes pancreatic cancer cells to radiation through the Wnt/β-catenin pathway[J]. Oncogene,2018,37(7):953-962.DOI:10.1038/onc.2017.401.