Li Yong, Wu Changqiang, Chen Tianwu, Zhang Juanjuan, Liu Gang, Pu Yu, Zhu Jiang, Shen Chengyi, Zhang Yang, Zeng Nanlin, Zhang Xiaoming
Sichuan Key Laboratory of Medical Imaging and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Sichuan Key Laboratory of Medical Imaging and School of Medical Imaging, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Oncol Rep. 2016 Dec;36(6):3449-3455. doi: 10.3892/or.2016.5152. Epub 2016 Oct 6.
It was previously demonstrated that mucin 4 (MUC4) is not expressed in normal pancreatic tissues or in chronic pancreatitis tissue but is highly expressed in pancreatic cancer (PC) tissue. Effective MUC4 gene knockdown in PC may contribute to the elucidation of pancreatic tumor development and metastasis, and may be valuable in new therapeutic approaches. Thus to confirm this, in the present study, the BxPC-3 cell line was transfected with eight pairs of shRNA lentiviral vectors for MUC4. The qPCR results showed that expression of MUC4 mRNA in the BxPC-3 cells was significantly decreased at 96 h after transfection. One of these shRNA lentiviral vectors (shRNA‑A141) had showed the strongest suppressive effect on MUC4 mRNA expression and was used for MUC4 knockdown in BxPC-3 cells. After stable transfection, BxPC-3 cells showed a significantly lower expression of MUC4 mRNA and MUC4 protein, and were suppressed on cell growth and migration. In vivo, lower tumor growth rates and tumor volume were observed in the tumors derived from the MUC4-knockdown cells, whereas the transplanted tumors derived from the control group cells, grew rapidly. Thus, inhibition of MUC4 expression may be an effective means for mitigating metastasis and invasion of PC.
先前的研究表明，黏蛋白4（MUC4）在正常胰腺组织或慢性胰腺炎组织中不表达，但在胰腺癌（PC）组织中高表达。在PC中有效敲低MUC4基因可能有助于阐明胰腺肿瘤的发生和转移，并且在新的治疗方法中可能具有价值。因此，为了证实这一点，在本研究中，用八对针对MUC4的shRNA慢病毒载体转染BxPC-3细胞系。qPCR结果显示，转染后96小时，BxPC-3细胞中MUC4 mRNA的表达显著降低。其中一种shRNA慢病毒载体（shRNA‑A141）对MUC4 mRNA表达的抑制作用最强，并用于在BxPC-3细胞中敲低MUC4。稳定转染后，BxPC-3细胞中MUC4 mRNA和MUC4蛋白的表达显著降低，细胞生长和迁移受到抑制。在体内，源自MUC4敲低细胞的肿瘤生长速率和肿瘤体积较低，而源自对照组细胞的移植肿瘤生长迅速。因此，抑制MUC4表达可能是减轻PC转移和侵袭的有效手段。
