辐射诱导pEgr-p16的表达及抑瘤作用的实验研究
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摘要
本研究根据电离辐射可诱导早期生长反应-1(Egr-1) 基因启动子激活，启
动下游基因表达的分子机制和抑癌基因p16的抑瘤作用，构建了含有放射敏感
性启动子Egr-1和人源性p16基因的重组表达质粒pEgr-p16。探讨了经pEgr-p16
重组质粒转染HeLa细胞和SMMC-7721细胞在60Coγ射线照射后，p16基因
的表达及其抑制肿瘤细胞生长中的作用。
体外实验研究证实：重组质粒pEgr-p16转染的HeLa细胞和SMMC-7721
细胞，接受60Coγ射线照射后p16表达明显高于未转染的HeLa细胞和
SMMC-7721细胞。进一步的研究表明：辐射可诱导pEgr-p16重组质粒转染的
HeLa细胞和SMMC-7721细胞CDK4、 CyclinD1蛋白表达下调；c-myc基因转
录水平下调。由于辐射诱导激活了Egr-1基因启动子，使p16及其相关下游基
因表达增强或下调，加之辐射的联合作用，引起HeLa细胞和SMMC-7721细
胞发生G2／M期阻滞，最终导致HeLa细胞和SMMC-7721细胞的增殖抑制。
本研究结果为探索新的肿瘤治疗方案、提高肿瘤放射治疗效果具有重要的
理论意义和实际意义。
ExPerimental study on exPression of PEgr-P16 and the role of
anti-tumor indueed by ionizing radiation
In this study， aeeording to the meehanism that ionizing radiation ean aetivate
early growth resPonse-1(Egr-l)gene Promoter，whieh induees the exPression of
downstream genes and anti-tumor effeet of a tumor suPPressor gene P16，thus，a
reeombinant Plasmid whieh eontaining human suPPressor gene P16 and
radio-sensitive Promoter(Egr-l)was eonstrueted.
It has been demonstrated that 6oeo-rays irradiation ean enhanee the
exPression of P16 in HeLa and SMMC-7721 eells whieh were transfeeted by
recombined Plasmids PEgr-P16 in vitro.It was higher than that in HeLa and
SMMC-772 1 eells whieh were not transfeeted.The researeh also demonstrated that
radiation ean deerease the exPression of CDK4 and CyelinD 1 Protein level and
deerease the exPression ofe-mye gene transeriPtional level in Hel，a eells and
SMMC-772 1 eells whieh were transfeeted by reeombined Plasmids PEgr-P16.The
inerease or deerease of exPression of P16 and eorrelative downstream genes
dePends on Egr-1 Promoter that aetivated by ionizing radiation.The
above-meniioned roles and radiation effeets indueed GZ/M arrest and inhibited eell
growth in HeLa and SMMC-7721 eells finally.
This researeh has an imPortant and Praetieal signifieanee for investigating new
theraPy method that inerease radiotherapeutie effeets on malignant tumor.
动下游基因表达的分子机制和抑癌基因p16的抑瘤作用，构建了含有放射敏感
性启动子Egr-1和人源性p16基因的重组表达质粒pEgr-p16。探讨了经pEgr-p16
重组质粒转染HeLa细胞和SMMC-7721细胞在60Coγ射线照射后，p16基因
的表达及其抑制肿瘤细胞生长中的作用。
体外实验研究证实：重组质粒pEgr-p16转染的HeLa细胞和SMMC-7721
细胞，接受60Coγ射线照射后p16表达明显高于未转染的HeLa细胞和
SMMC-7721细胞。进一步的研究表明：辐射可诱导pEgr-p16重组质粒转染的
HeLa细胞和SMMC-7721细胞CDK4、 CyclinD1蛋白表达下调；c-myc基因转
录水平下调。由于辐射诱导激活了Egr-1基因启动子，使p16及其相关下游基
因表达增强或下调，加之辐射的联合作用，引起HeLa细胞和SMMC-7721细
胞发生G2／M期阻滞，最终导致HeLa细胞和SMMC-7721细胞的增殖抑制。
本研究结果为探索新的肿瘤治疗方案、提高肿瘤放射治疗效果具有重要的
理论意义和实际意义。
ExPerimental study on exPression of PEgr-P16 and the role of
anti-tumor indueed by ionizing radiation
In this study， aeeording to the meehanism that ionizing radiation ean aetivate
early growth resPonse-1(Egr-l)gene Promoter，whieh induees the exPression of
downstream genes and anti-tumor effeet of a tumor suPPressor gene P16，thus，a
reeombinant Plasmid whieh eontaining human suPPressor gene P16 and
radio-sensitive Promoter(Egr-l)was eonstrueted.
It has been demonstrated that 6oeo-rays irradiation ean enhanee the
exPression of P16 in HeLa and SMMC-7721 eells whieh were transfeeted by
recombined Plasmids PEgr-P16 in vitro.It was higher than that in HeLa and
SMMC-772 1 eells whieh were not transfeeted.The researeh also demonstrated that
radiation ean deerease the exPression of CDK4 and CyelinD 1 Protein level and
deerease the exPression ofe-mye gene transeriPtional level in Hel，a eells and
SMMC-772 1 eells whieh were transfeeted by reeombined Plasmids PEgr-P16.The
inerease or deerease of exPression of P16 and eorrelative downstream genes
dePends on Egr-1 Promoter that aetivated by ionizing radiation.The
above-meniioned roles and radiation effeets indueed GZ/M arrest and inhibited eell
growth in HeLa and SMMC-7721 eells finally.
This researeh has an imPortant and Praetieal signifieanee for investigating new
theraPy method that inerease radiotherapeutie effeets on malignant tumor.
引文
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