CAJ | 학술논문

目的：探讨肾细胞癌（ RCC）中，地西他滨（ DAC）与紫杉醇（ PTX）相乘作用下的关键基因与分子机制。方法采用基因芯片技术和实时定量PCR筛选出二者联合应用于人肾癌细胞株ACHN及NC 65时的相乘相关基因，聚类分析观察基因的多种表达方式，IPA软件用于分析其中可能存在的信号转导通路及其中相关联的重要基因，Western blotting验证二者诱导的磷酸化PI3K、Akt的下调作用。结果对DAC联合PTX应用时发挥重要作用的诱导基因进行初步筛选并作验证，如淋巴增强因子1、转化生长因子β诱导基因、C-X-C基本向心体5和髓细胞组织增生病毒相关抑癌基因，同时参与DAC和PTX相乘作用的信号转导通路有PI3K/Akt信号通路、amb2整合信号通路、IL2调节信号通路及IL23调节信号通路。 PI3K/Akt及其他与细胞周期、DNA复制和细胞有丝分裂相关的一些信号转导通路也可能在其中发挥重要作用。结论 PI3K/Akt信号转导通路及多种基因参与了DAC与PTX的相乘作用，且该通路的激活状态可受到两种药物相乘作用的抑制。
목적：탐토신세포암（ RCC）중，지서타빈（ DAC）여자삼순（ PTX）상승작용하적관건기인여분자궤제。방법채용기인심편기술화실시정량PCR사선출이자연합응용우인신암세포주ACHN급NC 65시적상승상관기인，취류분석관찰기인적다충표체방식，IPA연건용우분석기중가능존재적신호전도통로급기중상관련적중요기인，Western blotting험증이자유도적린산화PI3K、Akt적하조작용。결과대DAC연합PTX응용시발휘중요작용적유도기인진행초보사선병작험증，여림파증강인자1、전화생장인자β유도기인、C-X-C기본향심체5화수세포조직증생병독상관억암기인，동시삼여DAC화PTX상승작용적신호전도통로유PI3K/Akt신호통로、amb2정합신호통로、IL2조절신호통로급IL23조절신호통로。 PI3K/Akt급기타여세포주기、DNA복제화세포유사분렬상관적일사신호전도통로야가능재기중발휘중요작용。결론 PI3K/Akt신호전도통로급다충기인삼여료DAC여PTX적상승작용，차해통로적격활상태가수도량충약물상승작용적억제。
Objective To investigate the gene transcriptional alteration and search for possible molecular mechanism and pathways implicated in the synergy of DAC and PTX against renal cell caroinoma( RCC) . Methods cDNA microarray was performed and coupled with real-time PCR to identify critical genes in the synergistic mechanism of both agents against RCC cells( ACHN and NC 65) . Various patterns of gene expression were observed by cluster analysis. IPA software was used to analyze possible biological path-ways and explore the inter-relationships between interesting network genes. Suppression of PI3K/Akt pathway by DAC and/or PTX was clarified by Western blotting. Results Several key regulatory genes were identified and confirmed, such as lymphoid enhancer factor 1, transforming growth factor β induced gene, C-X-C motif ligand 5 and myelocytomatosis viral related oncogene, and they may play a pivotal role in the synergy of DAC and PTX. The PI3K/Akt, amb2 Integrin, IL2-mediated and IL23-mediated pathways include in the synergy of DAC and PTX against RCC. Moreover, PI3K/Akt pathway and other pathways associated with cyclins, DNA replication and cell cycle/mitotic regulation were also associated with the synergy of DAC and PTX against RCC. Conclusion The activation of PI3K/Akt pathway and other genes may participate in the synergy of two agents. The PI3K/Akt pathway could be suppressed synergistically by two agents.