LAB-EXPERIMENTAL (PRE-CLINICAL) THERAPEUTICS AND PHARMACOLOGY
Authors: Fa H. Yang, Bo Zhang, Duo J. Zhou, Li Bie, Maxwell W. Tom, Daryl C. Drummond, Theodore Nicolaides, Sabine Mueller, Anuradha Banerjee, John W. Park, Michael D. Prados, David C. James, Nalin Gupta, Rintaro Hashizume, Garth W. Strohbehn, Jiangbing Zhou, Michael Fu, Toral R. Patel, Joseph M. Piepmeier, W. M. Saltzman, Qian Xie, Jennifer Johnson, Robert Bradley, Maria Libra Ascierto, Liang Kang, Julie Koeman, Francesco M. Marincola, Michael Briggs, Kirk Tanner, George F. Vande Woude, Shota Tanaka, Lindsay K. Klofas, Hiroaki Wakimoto, Darrell R. Borger, A. J. Iafrate, Tracy T. Batchelor, Andrew S. Chi, Achuthamangalam B. Madhankumar, Becky Slagle-Webb, Elias Rizk, Kimberly Harbaugh, James R. Connor, Gobinda Sarkar, Geoffry L. Curran, Robert B. Jenkins, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Manabu Onishi, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Isao Date, Karen Ebsworth, Matthew J. Walters, Linda S. Ertl, Yu Wang, Robert D. Berahovich, Penglie Zhang, Jay P. Powers, Shie-Chau Liu, Reem Al Omran, Timothy J. Sullivan, Juan C. Jaen, Martin Brown, Thomas J. Schall, Nitta Yusuke, Saki Shimizu, Yukiko Shishido-Hara, Yoshiaki Shiokawa, Motoo Nagane, Jie Wang, Ke Sai, Fu-Rong Chen, Zhong-Ping Chen, Zhendong Shi, Junxia Zhang, Kailiang Zhang, Lei Han, Luyue Chen, Xiaomin Qian, Anling Zhang, Guangxiu Wang, Zhifan Jia, Peiyu Pu, Chunsheng Kang, Ling-Yuan Kong, Tiffany A. Doucette, Sherise D. Ferguson, Jack Hachem, Yuhui Yang, Jun Wei, Waldemar Priebe, Gregory N. Fuller, Wei Qiao, Ganesh Rao, Amy B. Heimberger, Pin-Yuan Chen, Tomoko Ozawa, Daryl Drummond, Raquel Santos, Jacqueline D. Torre, Christina Ng, Edgar L. Lepe, Nicholas Butowski, Michael Prados, Krystof Bankiewicz, C. David James, Zhixiang Cheng, Yuanying Gong, Yufang Ma, Susanne Müller-Knapp, Stefan Knapp, Jialiang Wang, E. Antonio Chiocca, Balveen Kaur, John S. Yu, Valeria Judkowski, Alcinette Bunying, Jianfei Ji, Zhenhua Li, James Bender, Clemencia Pinilla, Vasisht Srinivasan, Marissa Dombovy-Johnson, Eleanor Carson-Walter, Kevin Walter, Zhiyuan Xu, Britney Popp, David Schlesinger, Lloyd Gray, Jason Sheehan, Stephen T. Keir, Henry S. Friedman, Darell D. Bigner, Carmen Kut, Betty Tyler, Elliot McVeigh, Xingde Li, Daniel Herzka, Stuart Grossman, Joseph L. Lasky, Yuntao Wang, Eduard Panosyan, W Hans Meisen, Jayson Hardcastle, Jeffrey Wojton, Eric Wohleb, Christopher Alvarez-Breckenridge, Michal Nowicki, Jonathan Godbout, Sang Y. Lee, Jonas M. Sheehan, Shaoman Yin, Stefan Kaluz, Saroja N. Devi, Rita de Noronha, Kyriakos C. Nicolaou, Erwin G. Van Meir, Jean E. Lachowicz, Michel Demeule, Christian Che, Sasmita Tripathy, Scott Jarvis, Jean-Christophe Currie, Anthony Regina, Tran Nguyen, Jean-Paul Castaigne, Katarzyna Zielinska-Chomej, Chitralekha Mohanty, Kristina Viktorsson, Rolf Lewensohn, James J. Driscoll, Samer Alsidawi, Ronald E. Warnick, Olivier Rixe, Ana C. deCarvalho, Susan Irtenkauf, Laura Hasselbach, Hong Xin, Tom Mikkelsen, Jonathan H. Sherman, Alan Siu, Olga Volotskova, Michael Keidar, Denise M. Gibo, Peter Dickinson, John Robertson, John Rossmeisl, Waldemar Debinski, Smita Nair, Robert Schmittling, David Boczkowski, Gerald Archer, John H. Sampson, Duane A. Mitchell, Ian S. Miller, Sebastien Didier, David W. Murray, Magimairajan Issaivanan, Salvatore J. Coniglio, Jeffrey E. Segall, Yousef Al-Abed, Marc Symons, Abbas Fotovati, Kaiji Hu, Hiro Wakimoto, Joanna Triscott, Jeffrey Bacha, Dennis M. Brown, Sandra E. Dunn, David J. Daniels, Tim E. Peterson, Allan B. Dietz, Gaylord J. Knutson, Ian F. Parney, Roberto J. Diaz, Brian Golbourn, Daniel Picard, Christian Smith, Annie Huang, James Rutka, Norihiko Saito, Jun Fu, Jun Yao, Shuzhen Wang, Dimpy Koul, W.K. A. Yung, Ying Yuan, Erik P. Sulman, Howard Colman, Frederick F. Lang, Emily A. Slat, Erik D. Herzog, Joshua B. Rubin, Arthur S. Carminucci, Benjamin Amendolara, Richard Leung, Liang Lei, Peter Canoll, Jeffrey N. Bruce, Jeffrey A. Wojton, Zhengtao Chu, Chang-Hyuk Kwon, Lionel M. Chow, Mary Palascak, Robert Franco, Tristan Bourdeau, Sherry Thornton, Xiaoyang Qi, Gaspar J. Kitange, Ann C. Mladek, Dan Su, Brett L. Carlson, Mark A. Schroeder, Jenny L. Pokorny, Katrina K. Bakken, Shiv K. Gupta, Paul A. Decker, Wenting Wu, Jann N. Sarkaria, Marc P. Oddou, Alexis Mollard, Lee T. Call, Hariprasad Vakayalapati, Steven L. Warner, Sunil Sharma, David J. Bearss, Thomas C. Chen, Heeyeon Cho, Weijun Wang, Florence M. Hofman, Catherine T. Flores, David Snyder, Luis Sanchez-Perez, Christina Pham, Henry Friedman, Eric Woolf, Mohammed G. Abdelwahab, Gregory Turner, Mark C. Preul, Andrew Lynch, Jong M. Rho, Adrienne C. Scheck, Laurent Salphati, Timothy P. Heffron, Bruno Alicke, Kai Barck, Richard A. Carano, Jonathan Cheong, Joan Greve, Leslie B. Lee, Merry Nishimura, Jodie Pang, Emile G. Plise, Hani Bou Reslan, Xiaolin Zhang, Stephen G. GOuld, Alan G. Olivero, Heidi S. Phillips, Gelareh Zadeh, Shahrzad Jalali, David Voce, Zhang Wei, Kang Shijun, Khodarev Nikolai, Wahlstrom Josh, Crawley Clayton, Yamini Bakhtiar, Ryan Alkins, Alison Burgess, Milan Ganguly, Winfried Wels, Kullervo Hynynen, Yan M. Li, Huang Jun, Vallera Daniel, Hall A. Walter, Hiroshi Nakashima, Tran T. Nguyen, Imran Shalkh, William F. Goins, E. A. Chiocca, Ilya V. Pyko, Mitsutoshi Nakada, Natsuki Furuyama, Teng Lei, Yutaka Hayashi, Kazuyuki Kawakami, Toshinari Minamoto, Aliaksandr S. Fedulau, Jun-ichiro Hamada
Journal: Neuro-Oncology (2012)

Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7+1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in theprogressionoftheM-phaseofthecellcycle.Itisassociatedwithseveralimportant pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.