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Exosomes-Coated miR-34a Displays Potent Antitumor Activity in Pancreatic Cancer Both in vitro and in vivo.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-25 , DOI: 10.2147/dddt.s265423 Ling Zuo 1 , Hongyu Tao 2 , Huanli Xu 2 , Cong Li 2 , Gan Qiao 1, 3 , Mingyue Guo 1 , Shousong Cao 1 , Minghua Liu 1 , Xiukun Lin 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-25 , DOI: 10.2147/dddt.s265423 Ling Zuo 1 , Hongyu Tao 2 , Huanli Xu 2 , Cong Li 2 , Gan Qiao 1, 3 , Mingyue Guo 1 , Shousong Cao 1 , Minghua Liu 1 , Xiukun Lin 1
Affiliation
Purpose: MiR-34a, which acts as an important tumor suppressor gene, plays an important role in pancreatic cancer. However, the therapeutic application of miR-34a is limited by the lack of an effective delivery system. In the present study, we synthesize exosomes-coated miR-34a (exomiR-34a), and the anticancer effect of exomiR-34a was evaluated in pancreatic cancer.
Materials and Methods: An ultrasound approach was used to synthesize exomiR-34a, and its transfection efficiency was examined by confocal microscopy and flow cytometry. The level of miR-34a and its targeted gene Bcl-2 was detected by real-time quantitative PCR (qRT-PCR). MTT analysis was performed to determine the effect of exomiR-34a on the growth of pancreatic cancer cells. Annexin-V/PI double staining and Western blot analysis were carried out to determine the apoptosis of the pancreatic cancer cells. The xenograft nude mice model bearing human pancreatic cancer Panc28 cells was used to determine the antitumor effect of exomiR-34a in vivo.
Results: The exomiR-34a could cross the cell membrane efficiently, and downregulated the expression of the targeted gene Bcl-2. Treatment with exomiR-34a inhibited the growth of the pancreatic cancer cells significantly and the nanoparticles also induced apoptosis in cancer cells via affecting the expression of apoptotic-related genes. In vivo study using xenograft nude mice bearing Panc28 cancer cells revealed that exomiR-34a suppressed the growth of tumors significantly.
Conclusion: ExomiR-34a can inhibit the growth of pancreatic cancer both in vitro and in vivo. Targeting miR-34a is a promising strategy for the treatment of pancreatic cancer. ExomiR-34a has the potential to be developed as a novel anticancer agent for the treatment of human pancreatic malignancy.
Keywords: pancreatic cancer, miR-34a, exosomes, Bcl-2, anticancer
中文翻译：
外泌体包被的 miR-34a 在体外和体内均显示出有效的胰腺癌抗肿瘤活性。
目的： MiR-34a作为重要的抑癌基因，在胰腺癌中发挥重要作用。然而，由于缺乏有效的递送系统，miR-34a 的治疗应用受到限制。在本研究中，我们合成了外泌体包被的 miR-34a (exomiR-34a)，并评估了 exomiR-34a 在胰腺癌中的抗癌作用。
材料和方法：使用超声方法合成exomiR-34a，并通过共聚焦显微镜和流式细胞术检查其转染效率。通过实时定量PCR（qRT-PCR）检测miR-34a及其靶基因Bcl-2的水平。进行MTT分析以确定exomiR-34a对胰腺癌细胞生长的影响。采用Annexin-V/PI双染和Western blot分析检测胰腺癌细胞的凋亡情况。使用带有人胰腺癌Panc28细胞的异种移植裸鼠模型来确定exomiR-34a在体内的抗肿瘤作用。
结果：exomiR-34a可以有效地穿过细胞膜，下调靶基因Bcl-2的表达。exomiR-34a治疗显着抑制胰腺癌细胞的生长，纳米颗粒还通过影响凋亡相关基因的表达诱导癌细胞凋亡。使用携带 Panc28 癌细胞的异种移植裸鼠的体内研究表明，exomiR-34a 显着抑制了肿瘤的生长。
结论： ExomiR-34a在体外和体内均能抑制胰腺癌的生长。靶向 miR-34a 是一种很有前景的胰腺癌治疗策略。ExomiR-34a 有可能被开发为一种用于治疗人类胰腺恶性肿瘤的新型抗癌剂。
关键词：胰腺癌，miR-34a，外泌体，Bcl-2，抗癌
更新日期：2020-08-25
Materials and Methods: An ultrasound approach was used to synthesize exomiR-34a, and its transfection efficiency was examined by confocal microscopy and flow cytometry. The level of miR-34a and its targeted gene Bcl-2 was detected by real-time quantitative PCR (qRT-PCR). MTT analysis was performed to determine the effect of exomiR-34a on the growth of pancreatic cancer cells. Annexin-V/PI double staining and Western blot analysis were carried out to determine the apoptosis of the pancreatic cancer cells. The xenograft nude mice model bearing human pancreatic cancer Panc28 cells was used to determine the antitumor effect of exomiR-34a in vivo.
Results: The exomiR-34a could cross the cell membrane efficiently, and downregulated the expression of the targeted gene Bcl-2. Treatment with exomiR-34a inhibited the growth of the pancreatic cancer cells significantly and the nanoparticles also induced apoptosis in cancer cells via affecting the expression of apoptotic-related genes. In vivo study using xenograft nude mice bearing Panc28 cancer cells revealed that exomiR-34a suppressed the growth of tumors significantly.
Conclusion: ExomiR-34a can inhibit the growth of pancreatic cancer both in vitro and in vivo. Targeting miR-34a is a promising strategy for the treatment of pancreatic cancer. ExomiR-34a has the potential to be developed as a novel anticancer agent for the treatment of human pancreatic malignancy.
Keywords: pancreatic cancer, miR-34a, exosomes, Bcl-2, anticancer
中文翻译：
外泌体包被的 miR-34a 在体外和体内均显示出有效的胰腺癌抗肿瘤活性。
目的： MiR-34a作为重要的抑癌基因，在胰腺癌中发挥重要作用。然而，由于缺乏有效的递送系统，miR-34a 的治疗应用受到限制。在本研究中，我们合成了外泌体包被的 miR-34a (exomiR-34a)，并评估了 exomiR-34a 在胰腺癌中的抗癌作用。
材料和方法：使用超声方法合成exomiR-34a，并通过共聚焦显微镜和流式细胞术检查其转染效率。通过实时定量PCR（qRT-PCR）检测miR-34a及其靶基因Bcl-2的水平。进行MTT分析以确定exomiR-34a对胰腺癌细胞生长的影响。采用Annexin-V/PI双染和Western blot分析检测胰腺癌细胞的凋亡情况。使用带有人胰腺癌Panc28细胞的异种移植裸鼠模型来确定exomiR-34a在体内的抗肿瘤作用。
结果：exomiR-34a可以有效地穿过细胞膜，下调靶基因Bcl-2的表达。exomiR-34a治疗显着抑制胰腺癌细胞的生长，纳米颗粒还通过影响凋亡相关基因的表达诱导癌细胞凋亡。使用携带 Panc28 癌细胞的异种移植裸鼠的体内研究表明，exomiR-34a 显着抑制了肿瘤的生长。
结论： ExomiR-34a在体外和体内均能抑制胰腺癌的生长。靶向 miR-34a 是一种很有前景的胰腺癌治疗策略。ExomiR-34a 有可能被开发为一种用于治疗人类胰腺恶性肿瘤的新型抗癌剂。
关键词：胰腺癌，miR-34a，外泌体，Bcl-2，抗癌
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