ADENOVIRAL TRANSFER OF FHIT GENE TO LUNG CANCER

FHIT 基因的腺病毒转移至肺癌

• 批准号: 11670594
• 负责人: KOJIMA Akira
• 金额: $ 1.66万
• 依托单位: JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670594/
• 关键词: LUNG CANCER; FHIT GENE; GENE THERAPY

TO EVALUATE THE CONCEPT THAT IN VIVO TRANSFER OF THE HUMAN FHIT GENE WILL SUPPRESS THE LUNG CANCER CELLS, WE CONSTRUCTED AN ADENOVIRUS VECTOR (AdCMVFHIT) CARRYING THE HUMAN FHIT GENE DRIVEN BY THE CMV PROMOTOR.THE EXPRESSION OF THE FHIT cDNA FOLLOWING IN VITRO TRANSFER WITH THE AdCMVFHIT VECTOR WAS EVALUATED AT THE mRNALEVEL.NORTHERN ANALYSIS REVEALED mRNA TRANSCRIPTS OF THE FHIT cDNA IN A549 CELLS.IN ADDITION, HPLC ANALYSIS SHOWED FUNCTIONAL FHIT PROTEIN RESPONDED WITH AR3A.WE EVALUATED THE GROWTH OF A549 CELLS FOLLOWING INFECTION WITH AdCMVFHIT IN VITRO.THE INFECTED CELLS WERE SIGNIFICANTLY SUPPRESSED IN COMPARISON WITH CONTROL (P<0.05).CONSISTENT WITH THESE IN VITRO OBSERVATIONS, WHEN AdCMVFHIT WAS DIRECTLY INJECTED INTO ESTABLISHED SUBCUTANEOUS A549 TUMORS IN NUDE MICE, THERE WAS 47% REDUCTION WITH IN TUMOR SIZE AT DAY 20 AND A 51% AT DAY 24 (P=0.023 AND P=0.013).THESE OBSERVATIONS SUGGEST THAT LOCAL GENE TRANSFER OF THE HUMAN FHIT GENE MAY HAVE POTENTIAL AS A STRATEGY FOR CONTROL OF GROWTH OF LUNG CANCER.

摘要为了验证人FHIT基因在体内的转移是否会抑制肺癌细胞，我们构建了一个由CMV启动子驱动的携带人FHIT基因的腺病毒载体（AdCMVFHIT）。用AdCMVFHIT载体体外转染后，在mrna水平上评价了FHIT cDNA的表达。NORTHERN分析在A549细胞中发现了FHIT cDNA的mRNA转录本。此外，HPLC分析显示功能性fhit蛋白与ar3a有应答。我们在体外评估了AdCMVFHIT感染后A549细胞的生长情况。与对照组相比，感染细胞明显受到抑制（p <0.05）。与这些体外观察结果一致，当AdCMVFHIT直接注射到裸鼠已建立的皮下A549肿瘤时，肿瘤大小在第20天和第24天分别减少了47%和51% （P=0.023和P=0.013）。这些观察结果表明，人类fhit基因的局部基因转移可能有潜力作为控制肺癌生长的策略。

项目成果

Kojima A., Morokawa N., Tanabe O., Eto Y., Yoshimura K.: "Adenoviral transfer of FHIT gene to lung cancer."The Journal of The Japanese Respiratory Society. 38. 130 (2000)

Kojima A.、Morokawa N.、Tanabe O.、Eto Y.、Yoshimura K.：“FHIT 基因的腺病毒转移至肺癌。”日本呼吸学会杂志。

Kojima A., Morokawa N., Aoki K., Anzai C., Eto Y., Yoshimura K.: "Adenoviral transfer of FHIT gene to lung cancer."Haigan. 40. 387 (2000)

Kojima A.、Morokawa N.、Aoki K.、Anzai C.、Eto Y.、Yoshimura K.：“FHIT 基因的腺病毒转移至肺癌。”Haigan。

児島章,諸川納早,田辺修,衛藤義勝,吉村邦彦: "肺癌に対するアデノウイルスベクターを用いたFHIT遺伝子導入"日本呼吸器学会雑誌. 38. 130 (2000)

Akira Kojima、Nosaya Morokawa、Osamu Tanabe、Yoshikatsu Eto、Kunihiko Yoshimura：“使用腺病毒载体进行肺癌的 FHIT 基因转移”日本呼吸学会杂志 38. 130 (2000)。

Kojima A., Morokawa N., Tanabe O., Anzai C., Eto Y., Yoshimura K.: "Suppression on growth of lung cancer cells by adenovirus mediated gene transfer of the human FHIT gene"American Journal of Respiratory and Critical Care Medicine. 161. A676 (2000)

Kojima A.、Morokawa N.、Tanabe O.、Anzai C.、Eto Y.、Yoshimura K.：“通过腺病毒介导的人类 FHIT 基因的基因转移抑制肺癌细胞的生长”美国呼吸与重症监护杂志