下调G蛋白信号调控因子2表达对胰腺癌细胞化疗敏感性的影响
| 作者: |
1郑伟,
1张建新,
1谭克,
1陈思澈,
1范逸怡,
1党胜春
1 江苏大学附属医院 普通外科，江苏 镇江 212001 |
| 通讯: |
党胜春
Email: dscgu@163.com |
| DOI: | 10.3978/.2018.03.009 |
| 基金: | 江苏省六大高峰人才计划资助项目（WSN-007）。 |
摘要
目的：探讨下调G蛋白信号调控因子2（GPSM2）表达对胰腺癌细胞化疗敏感性的影响。
方法：构建GPSM2低表达的胰腺癌MIA-PaCa-2细胞并鉴定；将16只裸鼠随机均分为两组，分别皮下接种GPSM2低表达与自然表达的MIA-PaCa-2细胞构建荷瘤模型，两组中分别一半注射吉西他滨（100 mg/kg），一半注射等体积生理盐水（腹腔注射，3次/周，共注射4周），绘制瘤体生长曲线，并于末次注射后第3天处死裸鼠，测量肿瘤体积。
结果：成功构建GPSM2表达下调的MIA-PaCa-2细胞。移植瘤的生长速度与体积大小的趋势均表现为GPSM2自然表达+生理盐水组>GPSM2自然表达+吉西他滨组>GPSM2低表达+生理盐水组>GPSM2低表达+吉西他滨组。析因设计分析结果显示，单独吉西他滨或单独下调GPSM2基因表达对于抑制裸鼠瘤体生长的主效应均具有统计学意义（均P=0.000）；吉西他滨联合下调GPSM2基因表达对于抑制裸鼠瘤体生长的交互效应尚未达到统计学意义（P=0.073）；但吉西他滨联合下调GPSM2基因表达对于肿瘤生长的抑制作用相对于单独吉西他滨或单独下调GPSM2基因表达的单独效应均有统计学意义（P=0.000、0.003）。
结论：下调GPSM2基因表达是否有增强胰腺癌细胞化疗敏感性的作用尚不确定，但下调GPSM2基因表达的同时予以化疗对胰腺癌生长的抑制效果明显强于两者单独作用。
关键词：
胰腺肿瘤；RGS蛋白质类；化疗；异种移植模型抗肿瘤试验
方法：构建GPSM2低表达的胰腺癌MIA-PaCa-2细胞并鉴定；将16只裸鼠随机均分为两组，分别皮下接种GPSM2低表达与自然表达的MIA-PaCa-2细胞构建荷瘤模型，两组中分别一半注射吉西他滨（100 mg/kg），一半注射等体积生理盐水（腹腔注射，3次/周，共注射4周），绘制瘤体生长曲线，并于末次注射后第3天处死裸鼠，测量肿瘤体积。
结果：成功构建GPSM2表达下调的MIA-PaCa-2细胞。移植瘤的生长速度与体积大小的趋势均表现为GPSM2自然表达+生理盐水组>GPSM2自然表达+吉西他滨组>GPSM2低表达+生理盐水组>GPSM2低表达+吉西他滨组。析因设计分析结果显示，单独吉西他滨或单独下调GPSM2基因表达对于抑制裸鼠瘤体生长的主效应均具有统计学意义（均P=0.000）；吉西他滨联合下调GPSM2基因表达对于抑制裸鼠瘤体生长的交互效应尚未达到统计学意义（P=0.073）；但吉西他滨联合下调GPSM2基因表达对于肿瘤生长的抑制作用相对于单独吉西他滨或单独下调GPSM2基因表达的单独效应均有统计学意义（P=0.000、0.003）。
结论：下调GPSM2基因表达是否有增强胰腺癌细胞化疗敏感性的作用尚不确定，但下调GPSM2基因表达的同时予以化疗对胰腺癌生长的抑制效果明显强于两者单独作用。
Effect of down-regulating G protein signal regulating protein 2 expression on chemotherapy sensitivity of pancreatic cancer cells
CorrespondingAuthor:DANG Shengchun Email: dscgu@163.com
Abstract
Objective: To investigate the effect of down-regulating G protein signal regulating protein 2 (GPSM2) expression on chemotherapy sensitivity of pancreatic cancer cells.
Methods: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were constructed and identified. Sixteen nude mice were equally randomized into two groups, and were subcutaneously implanted with MIA-PaCa-2 cells with low GPSM2 expression and MIA-PaCa-2 cells with natural GPSM2 expression to establish the tumor-bearing models. After that, half mice underwent gemcitabine injection (100 mg/kg) and half mice were given saline of the same volume in each group (intraperitoneal injection, 3 times per week for 4 weeks). The tumor growth curves were drawn, and all mice were sacrificed on the third day after the last injection, and the volumes of the tumor xenografts were determined.
Results: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were successfully created. Both growth speed and volume of the tumor xenografts presented a decreasing trend as natural GPSM2 expression plus saline group>natural GPSM2 expression plus gemcitabine group>low GPSM2 expression plus saline group>low GPSM2 expression plus gemcitabine group. The result of factorial design showed that the main effect of either gemcitabine alone or down-regulating GPSM2 gene expression alone on tumor growth inhibition had statistical significance (both P=0.000), while the interaction effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition did not reach a statistical significance (P=0.073), but the simple effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition had statistical significance compared with gemcitabine alone or down-regulating GPSM2 gene expression alone (P=0.000 and 0.003).
Conclusion: Whether down-regulating GPSM2 gene expression will enhance chemotherapy sensitivity of pancreatic cancer cells cannot be confirmed. However, the inhibitory effect of down-regulating GPSM2 gene expression with simultaneous chemotherapy on pancreatic cancer is remarkably greater than that of their single actions.
Keywords：
Pancreatic Neoplasms; RGS Proteins; Chemotherapy; Xenograft Model Antitumor Assays
Methods: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were constructed and identified. Sixteen nude mice were equally randomized into two groups, and were subcutaneously implanted with MIA-PaCa-2 cells with low GPSM2 expression and MIA-PaCa-2 cells with natural GPSM2 expression to establish the tumor-bearing models. After that, half mice underwent gemcitabine injection (100 mg/kg) and half mice were given saline of the same volume in each group (intraperitoneal injection, 3 times per week for 4 weeks). The tumor growth curves were drawn, and all mice were sacrificed on the third day after the last injection, and the volumes of the tumor xenografts were determined.
Results: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were successfully created. Both growth speed and volume of the tumor xenografts presented a decreasing trend as natural GPSM2 expression plus saline group>natural GPSM2 expression plus gemcitabine group>low GPSM2 expression plus saline group>low GPSM2 expression plus gemcitabine group. The result of factorial design showed that the main effect of either gemcitabine alone or down-regulating GPSM2 gene expression alone on tumor growth inhibition had statistical significance (both P=0.000), while the interaction effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition did not reach a statistical significance (P=0.073), but the simple effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition had statistical significance compared with gemcitabine alone or down-regulating GPSM2 gene expression alone (P=0.000 and 0.003).
Conclusion: Whether down-regulating GPSM2 gene expression will enhance chemotherapy sensitivity of pancreatic cancer cells cannot be confirmed. However, the inhibitory effect of down-regulating GPSM2 gene expression with simultaneous chemotherapy on pancreatic cancer is remarkably greater than that of their single actions.