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Administration of PLGA nanoparticles carrying shRNA against focal adhesion kinase and CD44 results in enhanced antitumor effects against ovarian cancer

Cancer Gene Therapy volume 20, pages 242–250 (2013)Cite this article

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Abstract

The two membrane-bound proteins, focal adhesion kinase (FAK) and CD44, are involved in processes critical to cancer progression. FAK has an active role in angiogenesis, cell proliferation and cell apoptosis, whereas the heavily glycosylated CD44 has been implicated in cancer metastasis. Here, using short hairpin RNA (shRNA) against FAK and CD44, we demonstrate that simultaneous knockdown of both these genes inhibits cancer growth more efficiently than knockdown of either gene individually. Plasmids targeting these genes or non-relative control sequences were constructed and delivered to ovarian cancer targets by biodegradable poly D,L-lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Single gene knockdown resulted in significantly smaller tumors than those observed in the empty-vector control (P’s<0.001). More importantly, knockdown of both genes resulted in tumors smaller than both the empty-vector group (P<0.0001) and the single gene knockdown groups (P’s<0.001). Knockdown of both FAK and CD44 resulted in tumors with inhibited angiogenesis, reduced proliferation and increased apoptosis as compared with controls (P’s<0.001) and single knockdown groups (P’s<0.05). These results indicate that dual knockdown of FAK and CD44 in the tumors of patients with ovarian cancer may have an enhanced therapeutic effect, and point toward a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis.

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Acknowledgements

This work was kindly supported by grants from the National 973 Basic Research Programs of China (2011CB910703 and 2004CB518800) and Natural Science Foundation (0040215401068).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China

    L Zou, T Yi, Z Li, Y Bai, Q Zhong & X Zhao

  2. State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People’s Republic of China

    X Song, S Li, H Deng, X Chen & Y Wei

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  1. L Zou
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  2. X Song
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Correspondence to X Zhao.

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Zou, L., Song, X., Yi, T. et al. Administration of PLGA nanoparticles carrying shRNA against focal adhesion kinase and CD44 results in enhanced antitumor effects against ovarian cancer. Cancer Gene Ther 20, 242–250 (2013). https://doi.org/10.1038/cgt.2013.12

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  • DOI: https://doi.org/10.1038/cgt.2013.12

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