Ruilong Lan1,2,3, Fei Huang1,2,3, Guangxian Zhong4, Ruiqing Chen1,2,3, Zeng Wang1,2,3, Junying Chen1,2,3, Lengxi Fu1,2,3, Jinsheng Hong5, Lurong Zhang1,2,3. 1. a Central Lab , First Affiliated Hospital of Fujian Medical University , Fuzhou , China. 2. b Fujian Key Lab of Individualized Active Immunotherapy , Fuzhou , China. 3. c Key Laboratory of Radiation Biology of Fujian Province Universities , Fuzhou , China. 4. d Department of Orthopaedics , First Affiliated Hospital of Fujian Medical University , Fuzhou , China. 5. e Department of Radiotherapy , First Affiliated Hospital of Fujian Medical University , Fuzhou , China.
Abstract
PURPOSE: Radioresistance is an important factor for unsatisfactory prognosis in Nasopharyngeal carcinoma (NPC) patients. Ubiquitous mitochondrial creatine kinase (CKMT1) is always associated with malignancy in a variety of cancers. However, its significance in NPC progression and radiosensitivity remains unclear. The present study focused on investigating the effects of CKMT1 on NPC cell radiosensitivity. MATERIAL AND METHODS: CKMT1 was overexpressed in NPC cell line CNE-1 or knocked out in CNE-2. Biological changes were detected after cells exposing to different doses of X-ray to determine the role of CKMT1 on NPC cell radiosensitivity. RESULTS: CKMT1 promotes proliferation and migration in NPC cell lines CNE-1 and CNE-2. Overexpression of CKMT1 in CNE-1 cells enhanced colony formation rates, reduced G2/M phase cell cycle arrest, lowered apoptosis rate and c-PARP level, and elevated STAT3 phosphorylation level after radiation treatment. While knocking out CKMT1 using the CRISPR/Cas9 system in CNE-2 cells lowered colony formation rates, increased G2/M phase cell cycle arrest, apoptosis rates, and c-PARP levels, and decreased STAT3 phosphorylation in response to radiation treatment. CONCLUSIONS: NPC cells with higher CKMT1 exhibited lower radiosensitivity through promoting phosphorylation of STAT3. Our findings suggest that CKMT1 may be an alternative radiotherapeutic target in NPC therapy.
PURPOSE: Radioresistance is an important factor for unsatisfactory prognosis in Nasopharyngeal carcinoma (NPC) patients. Ubiquitous mitochondrial creatine kinase (CKMT1) is always associated with malignancy in a variety of cancers. However, its significance in NPC progression and radiosensitivity remains unclear. The present study focused on investigating the effects of CKMT1 on NPC cell radiosensitivity. MATERIAL AND METHODS:CKMT1 was overexpressed in NPC cell line CNE-1 or knocked out in CNE-2. Biological changes were detected after cells exposing to different doses of X-ray to determine the role of CKMT1 on NPC cell radiosensitivity. RESULTS:CKMT1 promotes proliferation and migration in NPC cell lines CNE-1 and CNE-2. Overexpression of CKMT1 in CNE-1 cells enhanced colony formation rates, reduced G2/M phase cell cycle arrest, lowered apoptosis rate and c-PARP level, and elevated STAT3 phosphorylation level after radiation treatment. While knocking out CKMT1 using the CRISPR/Cas9 system in CNE-2 cells lowered colony formation rates, increased G2/M phase cell cycle arrest, apoptosis rates, and c-PARP levels, and decreased STAT3 phosphorylation in response to radiation treatment. CONCLUSIONS: NPC cells with higher CKMT1 exhibited lower radiosensitivity through promoting phosphorylation of STAT3. Our findings suggest that CKMT1 may be an alternative radiotherapeutic target in NPC therapy.