ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer
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RESEARCH ARTICLE
Open Access
ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer Tingting Yao1,2†, Xueling Weng1†, Yao Yao3, Chunxian Huang1, Jing Li1, Yongpai Peng1, Rongchun Lin1* and Zhongqiu Lin1*
Abstract Background: We have previously found there was a small subpopulation of cells with cancer stem cell-like phenotype ALDH-1 in cervical cancer. Radiotherapy has been applied in most of the cervical cancer. However,the mechanisms underlying radioresistance still remained elusive. Our study is to explore whether ALDH+ cell promotes radioresistance by hypoxia. Methods: Cells were respectively cultured in hypoxia and normoxia environment and analyzed for marker stability, and cell cycle distribution. Results: Cell growth, apoptosis, cell cycle, sphere formation were affected by hypoxia. ALDH-1 and CHK2 were upregulated after hypoxia. Conclusions: Here we show that ALDH-1 positive cells contribute to cervical carcinoma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of these cells is enriched after radiation in cervical carcinoma. Keywords: Cervical carcinoma, ALDH-1, Radioresistance, Hypoxia
Background Cervical cancer is the second most frequent cancer in female worldwide, and radiotherapy (RT) has been considered as the key treatment modality for cervical carcinoma. More than 60% of cervical cancer patients have chosen radiotherapy as treatment [1]. Although improvement of control and survival has been shown after simultaneous chemo-radiation [2–4], impaired RT response is a major clinical problem in several solid tumor types including cervical carcinoma. As for advanced cervical cancer, nearly half of them got RT
* Correspondence: [email protected]; [email protected] † Tingting Yao and Xueling Weng are the co-first authors. 1 Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang West Road, Guangzhou 510120, People’s Republic of China Full list of author information is available at the end of the article
failure [5]. Therefore, new therapeutic approaches are needed to settle the radioresistance. Most solid tumors have been identified with different oxygen areas [6]. Hypoxia is characterized by a hypoxic state, which is common in malignant tumors [7]. Hypoxia causes therapeutic resistance especially for radiotherapy. Hypoxia could generate reactive oxygen species and change the expression of proteins related to the repair of double stranded DNA and then dysregulating cell cycle checkpoint control leading to an abnormal DNA repair pathways [8–10]. These various effects related to hypoxia may help protect and maintain the cancer stem cell phenotype, thereby promoting tumor recurrence after treatment [11]. In our previous study, we found cervical cancer contains a small subpopulation of cells which may be associated with a cancer stem cell-like phenotype ALDH-1
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