Carcinogenesis, Teratogenesis & Mutagenesis ›› 2016, Vol. 28 ›› Issue (4): 262-268.doi: 10.3969/j.issn.1004-616x.2016.04.003

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Effects of protein phosphatase 2A inhibition on radiosensitivity of nasopharyngeal carcinoma

LÜ Peng1,2,6, MAN Qizhong3, WANG Yue4, ZHUANG Zhengping5, WANG Aiping1, ZENG Yixin6   

  1. 1. The New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China;
    2. Chinese Medical Journal, Chinese Medical Association Publishing House, Beijing 100710, China;
    3. Department of Anatomy, Shandong Wanjie Medical College, Zibo 255213, Shandong, China;
    4. Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, China Food and Drug Administration, Beijing 100050, China;
    5. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda 20892, USA;
    6. Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
  • Received:2016-04-16 Revised:2016-06-04 Online:2016-07-31 Published:2016-07-31

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Abstract: OBJECTIVE: To investigate the radiosensitizing effect of protein phosphatase 2A(PP2A) inhibition on nasopharyngeal carcinoma cell line CNE2 and its xenografts. METHODS: The cells and subcutaneous xenografts in BALB/c nude mice were randomly divided into control, norcantharidin (40 μmmol/L in vitro, 27 μmol/kg in vitro), irradiation (8 Gy in vitro, 20 Gy in vitro), and combination of norcantharidin and irradiation groups. MTT, Co-immunoprecipitation and flow cytometry were used to examine the effect of PP2A inhibition, cell cycle analysis, apoptosis of CNE2 and its xenografts by norcantharidin and (or) irradiation. RESULTS: We measured PP2A activity in CNE2 cells and xenografts 5 hours after exposure to 8 Gy radiation in vitro and 20 Gy radiation in vivo, with and without prior exposure to NCTD. Compared with control group, NCTD alone was associated with decreasedin PP2A activity of 70% in vitro and in vivo both. Radiation alone was associated with increased in PP2A activity of 210% and 165% in vitro and in vivo, respectively. The cell cycle arrested in G2/M and increasing of apoptotic ratio in CNE2 cells were significantly different between the control and the both two treatment alone groups (P<0.05). Compared with control group, the combination of 8 Gy and 40 μmol/L norcantharidin produced significant inhibition of PP2A(80% in vitro and 72% in vitro compared to control), accumulation of cells in G2/M-phase (87.88%±2.10%) and more apoptosis (77.15%±7.62%) in CNE2 cell lines compared to norcantharidin alone and radiation alone. Norcantharidin in combination with radiation produced the greatest effects on tumor growth slowing and decreasing tumor weight by 87.98% relative to control in CNE2 xenografts(compared to control, P<0.05). Furthermore, more apoptosis, necrotic cells and formation of apoptotic bodies were found in pathological section in norcantharidin plus radiotherapy group. CONCLUSION: PP2A might be a potential target for sensitization of nasopharyngeal carcinoma to radiatotherapy.

Key words: protein phosphatase 2A, norcantharidin, radiosensitizion, nasopharyngeal carcinoma

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