同步放化疗对宫颈鳞癌细胞增殖、凋亡及细胞周期的影响

The effects of radiotherapy and concurrent chemoradiotherapy on cell proliferation,apoptosis and cell cycle of cervical squamous carcinoma

目的:探讨局部晚期宫颈鳞癌细胞对同步放化疗应答的分子机制。方法:49例患者被分为2组:单纯放疗组(RT)和同步放化疗组(CCRT)。在治疗前和治疗中[RT组:放疗10 Gy后;CCRT组:放疗10 Gy+(DDP+5-FU)×1个周期]分别活检留取标本,用FCM、TUNEL及免疫组化检测细胞周期、凋亡以及PCNA的表达。结果:RT组和CCRT组治疗中较治疗前AI及凋亡阳性率均明显升高(P<0.05,P<0.001),治疗中CCRT组凋亡率显著高于RT组(P=0.03);PCNA的表达CCRT组较RT组降低更明显(P=0.005)。治疗中RT组细胞周期大部分被阻滞在G2/M期,而CCRT组大部分被同时阻滞在S和G2/M期。结论:CCRT治疗局部晚期宫颈鳞癌中化疗和放疗有协同作用,其机制可能为通过抑制细胞增殖以及阻滞细胞周期于S和G2/M期,使细胞周期同步化,继而诱导肿瘤细胞的凋亡实现的。

Objective： To clarify the molecular mechanism underlying the response of locally advanced cervical squamous carcinoma to radiotherapy or concurrent chemoradiotherapy. Methods： Forty-nine patients were divided in to two groups. The 25 patients in radiotherapy （RT） group were given radiotherapy alone. The 24 patients in the concurrent chemoradiotherapy （CCRT） group were given 3 cycles of chemotherapy （ DDP ＋5-FU） in addition with RT. The specimens of the cervical tumors were obtained by biopsy before and during the treatment （ 10 Gy irradiation for RT group and 10 Gy irradiation plus one cycle of DDP ＋ 5-FU chemotherapy for CCRT group）. The cell cycle distribution was analyzed by flow cytometry （FCM）. The apoptosis and PCNA expression in both groups were detected by TUNEL and immunohistochemical methods. Results： Apoptosis index （AI） and the positive rate of apoptosis were significantly increased after initiating RT and CCRT, respectively （ P 〈0.05, P 〈0. 001 ）. There were also marked reduction of PCNA after 1 week of RT and CCRT （P = 0. 000 and P = 0. 000）. The CCRT significantly increased the apoptosis rate and decreased PCNA expression than RT （P = 0.03 and P = 0. 005 ）. Most cervical cancer cells were arrested in G2/M phase during RT treatment. However, CCRT induced S and G2/M phase arrest in a majority of cervical carcinoma cells. Conclusions： The additive or synergistic effects between chemotherapy and radiotherapy may be the mechanism for the effect of CCRT on locally advanced cervical squamous carcinoma. CCRT induces apoptosis of tumor cells by inhibiting cell proliferation, inducing S and G2/M phase arrest, and synchronizing cell cycle.