AccScience Publishing / CP / Volume 1 / Issue 1 / DOI: 10.18063/cp.v1i1.214
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RESEARCH ARTICLE

A Novel Monoclonal Antibody PC322 Inhibit Prostate Cancer Cell Autophagy

Xing Kang1 Zhang Xu1 Xuejia Zhu1 Yuhan Yan2 Chong Li1,3,4,5*
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1 Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2 Department of Management Science and Engineering, School of Business, Renmin University of China, Beijing 100872, China
3 Beijing Jianlan Institute of Medicine, Beijing 100190, China
4 Beijing Zhongke Jianlan Biotechnology Co., Ltd., Beijing 101400, China
5 Guyuzhongke (Beijing) Medical Technology Co., Ltd., Beijing 100061, China
CP 2019, 1(1), 24–32; https://doi.org/10.18063/cp.v1i1.214
Received: 26 February 2019 | Accepted: 6 March 2019 | Published online: 15 March 2019
© 2019 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Autophagy is an important element in tumor progression. The clinical and commercial success of monoclonal antibodies (MAbs) for cancer has emerged as the fastest growing therapy. Prostate cancer is well appropriately suited for antibody therapy. PC322 is our newly prepared prostate cancer MAbs. In our current study, we described the impacts of PC322 on autophagy and biological behaviors in vitro and explored the possible mechanism of PC322 in prostate cancer cell autophagy. Role of PC322 on autophagy of LNCaP and C4-2 cells was observed with fluorescence microscopy, western blotting, and flow cytometry. Further, the function of PC322 on biological behaviors of prostate cancer cells was detected by Cell Counting Kit-8 kit, Hoechst 33342, wound healing assay, and cell adhesion assay. Finally, we found that autophagy-related genes3 (ATG3) was upregulated with stimulation of rapamycin, while PC322 inhibited ATG3 expression. In summary, in vitro experiments demonstrated that the new MAb PC322 inhibits cell autophagy, proliferation, and metastasis of LNCaP and C4-2 cells, and promote their apoptosis. PC322 inhibits LC3 conversion and suppresses the formation of autophagosomes by reducing ATG3 expression. 

Keywords
prostate cancer
monoclonal antibody
autophagy
autophagosomes
autophagy-related genes3
References

Torre, L.A., et al., Global cancer statistics, 2012. CA Cancer J Clin, 2015. 65(2): p. 87-108.

Ferlay, J., et al., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015. 136(5): p. E359-86.

Borley, N. and M.R. Feneley, Prostate cancer: diagnosis and staging. Asian J Androl, 2009. 11(1): p. 74-80.

Partin, A.W., et al., Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology, 2001. 58(6): p. 843-8.

Attard, G., et al., Prostate cancer. The Lancet, 2016. 387(10013): p. 70-82.

Klotz, L., et al., Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol, 2010. 28(1): p. 126-31.

Selvadurai, E.D., et al., Medium-term outcomes of active surveillance for localised prostate cancer. Eur Urol, 2013. 64(6): p. 981-7.

Naponelli, V., et al., Roles of autophagy induced by natural compounds in prostate cancer. Biomed Res Int, 2015. 2015: p. 121826.

White, E. and R.S. DiPaola, The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 2009. 15(17): p. 5308-16.

Shintani, T. and D.J. Klionsky, Autophagy in health and disease: A double-edged sword. Science, 2004. 306(5698): p. 990-995.

Lozy, F. and V. Karantza, Autophagy and cancer cell metabolism. Semin Cell Dev Biol, 2012. 23(4): p. 395-401.

Dalby, K.N., et al., Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy, 2010. 6(3): p. 322-329.

Maycotte, P. and A. Thorburn, Autophagy and cancer therapy. Cancer Biology & Therapy, 2014. 11(2): p. 127-137.

Lara, P.N., Jr., et al., Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Cancer, 2004. 100(10): p. 2125-31.

Morris MJ, R.V., Kelly WK, HER-2 profiling and targeting in prostate carcinoma: a Phase II trial of trastuzumab alone and with paclitaxel. Cancer, 2002. 94: p. 980-986.

Mendelsohn, J. and J. Baselga, Epidermal growth factor receptor targeting in cancer. Semin Oncol, 2006. 33(4): p. 369-85.

Yang XD, R.L., Davis G, From XenoMouse technology to panitumumab (ABXEGF). The Oncogenomics Handbook, 2005: p. 647-657.

Ferrara, N., et al., Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov, 2004. 3(5): p. 391-400.

Reese DM, F.P., Corry M, A phase II trail of humanized anti-vascular endothelial growth factor antibody for the treatment of androgen-independent prostate cancer. Pros J, 2001. 3(2): p. 65-70.

Picus J, H.S., Rini B, The use of bevacizumab (B) with docetaxel (D) and estramustine (E) in hormone refractory prostate cancer (HRPC): initial results of CALGB 90006. Proc Am Soc Clin Oncol, 2003. 22: p. 393.

Maiuri, M.C., et al., Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 2007. 8(9): p. 741-52.

Mizushima, N., T. Yoshimori, and Y. Ohsumi, The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol, 2011. 27: p. 107-32.

Levine, B. and G. Kroemer, Autophagy in the pathogenesis of disease. Cell, 2008. 132(1): p. 27-42.

Itakura, E. and N. Mizushima, Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy, 2010. 6(6): p. 764-776.

Nguyen, H.G., et al., Targeting autophagy overcomes Enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model. Oncogene, 2014. 33(36): p. 4521-30.

Kenific, C.M., T. Wittmann, and J. Debnath, Autophagy in adhesion and migration. J Cell Sci, 2016. 129(20): p. 3685-3693.

Lee, E., et al., Autophagy is essential for cardiac morphogenesis during vertebrate development. Autophagy, 2014. 10(4): p. 572-87.

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Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing