Induction of apoptosis in gynecologic cancer cells by the soluble IGF-I receptor.

可溶性 IGF-I 受体诱导妇科癌细胞凋亡。

• 批准号: 10671544
• 负责人: HONGO Atsushi
• 金额: $ 1.92万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671544/
• 关键词: IGF-I receptor; IGF-I; transformation; tumorigenicity; apoptosis; chemosensitivity; bystander effect

1) In order to evaluate the anti-tumor effect of the IGF-I receptor blockage in gynecologic malignancies, We transfected an antisense mRNA expression vector into human cervical cancer derived cell lines, SiHa, HeLa S3, and C33A and established stable transformants. Introduction of the antisense slightly inhibited growth in mono-layer and makedly inhibited anchorage-independent growth in soft agar and tumorigenicity in nude mice. These results were presented at the 90th annual meeting of AACR (Philadelphia PA, USA) and published in Cancer Research.2) Then we tried to use the soluble IGF-I receptor with a bystander effect that would be an advantage in clinical applications. We stably transfected the soluble IGF-I receptor in human ovarian carcinoma derived cell line CaOV-3. The soluble receptor was detected as a 70kDa protein from total cell lysates as well as conditioned media. Anchorage-independent growth of the soluble IGF-I receptor clones was strongly inhibited and conditioned media from transfected clones showed bystander effects. Tumorigenicity in nude mice was abrogated in transfected clones and co-culture of the parental cells with transfected clones showed bystander effects in vivo. Chemosensitivity against paclitaxel was tested by clonogenic assay and transfected clones showed much higher sensitivities. Percentages of the apoptotic cells after paclitaxel treatment were significantly higher in transfected clones ; indicating the abrogation of the anti-apoptotic activity of the IGF-I receptor caused this effect. These results were presented at the 5th International Symposium on IGFs (Brighton, UK), the 92nd annual meeting of AACR (New Orleans LA, USA) and submitted for publication

1)为了评价IGF-I受体阻断剂在妇科恶性肿瘤中的抗肿瘤作用，我们将反义mRNA表达载体转染人宫颈癌细胞系SiHa、HeLa S3和C33 A，并建立稳定的转化子。反义核酸的导入对单层细胞生长有轻微抑制作用，对软琼脂非贴壁生长和裸鼠成瘤性有明显抑制作用。这些结果在AACR第90届年会（美国宾夕法尼亚州费城）上发表，并发表在《癌症研究》上。2）然后我们尝试使用具有旁观者效应的可溶性IGF-I受体，这在临床应用中将是一个优势。我们在人卵巢癌衍生细胞系CaOV-3中稳定转染可溶性IGF-I受体。可溶性受体被检测为来自总细胞裂解物以及条件培养基的70 kDa蛋白质。锚定非依赖性生长的可溶性IGF-I受体克隆被强烈抑制和转染克隆的条件培养基显示旁观者效应。在裸鼠中的致瘤性在转染的克隆中被废除，并且亲本细胞与转染的克隆的共培养在体内显示出旁观者效应。克隆形成试验检测转染细胞对紫杉醇的敏感性。紫杉醇处理后的凋亡细胞的凋亡率显着较高的转染克隆，表明废除的IGF-I受体的抗凋亡活性引起这种效果。这些结果在第五届IGF国际研讨会（英国布莱顿）、第92届AACR年会（美国路易斯安那州新奥尔良）上发表并提交出版

项目成果

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Yasunari Miyagi, Mitsuo Yoshinouchi, and Takafumi Kudo: "Down-Regulation of the Insulin-like Growth Factor I Receptor by Antisense RNA Can Reverse the Transformed Phenotype of Human Cervical Cancer Cell L

Keiichiro Nakamura、Atsushi Hongo、Junichi Kodama、Yasunari Miyagi、Mitsuo Yoshinouchi 和 Takafumi Kudo：“反义 RNA 下调胰岛素样生长因子 I 受体可以逆转人宫颈癌细胞 L 的转化表型

Atsushi Hongo, Keiichiro Nakamura, Mitsuo Yoshinouchi, and Takafumi Kudo.: "Downregulation of the insulin-like growth factor I receptor by antisense can reversetransformed phenotypes of HPV positive and negative human cervical cancer cell lines."Proceedin

Atsushi Hongo、Keiichiro Nakamura、Mitsuo Yoshinouchi 和 Takafumi Kudo.：“通过反义下调胰岛素样生长因子 I 受体可以逆转 HPV 阳性和阴性人宫颈癌细胞系的表型。”

Atsushi Hongo, Hiroyuki Kuramoto, and Takafumi Kudo.: "A Soluble Insulin-like Growth Factor I Receptor Inhibits Tumorigenicity of CaOV-3 Human Ovarian Cancer Cells with a Bystander Effect and Increases Their Chemosensitivity to Paclitaxel."Proceedings AAC

Atsushi Hongo、Hiroyuki Kuramoto 和 Takafumi Kudo.：“可溶性胰岛素样生长因子 I 受体通过旁观者效应抑制 CaOV-3 人卵巢癌细胞的致瘤性，并增加其对紫杉醇的化学敏感性。”AAC 会议记录

Kiichiro Nakamura, Atsushi Hongo, et al.: "Down-Regulaton of the Insulin-like Growth Factor I Receptor by Antisense RNA Can Reverse the Transformed Phenotype of Human Cervical Cancer Cell Lines"Cancer Research. 60. 760-765 (2000)

Kiichiro Nakamura、Atsushi Hongo 等人：“反义 RNA 下调胰岛素样生长因子 I 受体可以逆转人类宫颈癌细胞系的转化表型”癌症研究。

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Yasunari Miyagi, Mitsuo Yoshinouchi, and Takafumi Kudo.: "Down-Regulation of the Insulin-like Growth Factor I Receptor by Antisense RNA Can Reverse the Transformed Phenotype of Human Cervical Cancer Cell

Keiichiro Nakamura、Atsushi Hongo、Junichi Kodama、Yasunari Miyagi、Mitsuo Yoshinouchi 和 Takafumi Kudo.：“通过反义 RNA 下调胰岛素样生长因子 I 受体可以逆转人宫颈癌细胞的转化表型