Effect of Hsp90 Inhibitor KW-2478 on HepG2 Cells
-
Published:2020-02-07
Issue:18
Volume:19
Page:2231-2242
-
ISSN:1871-5206
-
Container-title:Anti-Cancer Agents in Medicinal Chemistry
-
language:en
-
Short-container-title:ACAMC
Author:
Chang Xiaomin1ORCID, Zhao Xuerong1, Wang Jianping1, Ding Shi2, Xiao Lijun1, Zhao Enhong3, Zheng Xin3
Affiliation:
1. Department of Immunology, Chengde Medical University, Chengde City, China 2. Department of Pharmacology, Chengde Medical University, Chengde City, China 3. The Third Department of Surgery, The Affiliated Hospital of Chengde Medical University, Chengde City, China
Abstract
Objective:
The objectives of this study were to investigate the effects of proliferation, apoptosis, cell
cycle, invasion, and senescence of KW-2478 on HepG2 cells, and to explore the related mechanism of apoptosis
and the cell cycle.
Methods:
HepG2 cells (hepatocellular carcinoma cells) were cultured with KW-2478, at different doses and for
different times, in vitro. The MTT assay was used to detect the effect of KW-2478 on proliferation of HepG2
cells. Flow cytometry was used to determine the effects of KW-2478 on the cell cycle and apoptosis of HepG2
cells. The Transwell assay was used to determine the effect of KW-2478 on cell invasion. The β-galactosidase
assay tested the effect of low-dose KW-2478 on the senescence of HepG2 cells. Western blotting and the quantitative
polymerase chain reaction were used respectively to assess changes in protein and mRNA levels of related
factors in HepG2 cells after the KW-2478 treatment.
Results:
KW-2478 significantly inhibited proliferation of HepG2 cells. KW-2478 induced apoptosis and cell
cycle arrest of HepG2 cells, and inhibited the invasion of HepG2 cells; low dose KW-2478 promoted HepG2
senescence.
Conclusions:
KW-2478 inhibited the proliferation of HepG2 cells, induced apoptosis and cell cycle arrest, inhibited
invasion, and promoted senescence. KW-2478 affected the expression of related factors in the mitochondrial
apoptotic signaling and cell cycle-related regulatory pathways. KW-2478 downregulated the expression of
STAT3, which is a key factor in the JAK-STAT pathway, indicating that KW-2478 may affect the function of
HepG2 cells by downregulating STAT3.
Funder
Department of Education of Hebei Province Chengde Medical University
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Reference23 articles.
1. Fitzmaurice C.; Dicker D.; Pain A.; Hamavid H.; Moradi-Lakeh M.; MacIntyre M.F.; Allen C.; Hansen G.; Woodbrook R.; Wolfe C.; Hamadeh R.R.; Moore A.; Werdecker A.; Gessner B.D.; Te Ao B.; McMahon B.; Karimkhani C.; Yu C.; Cooke G.S.; Schwebel D.C.; Carpenter D.O.; Pereira D.M.; Nash D.; Kazi D.S.; De Leo D.; Plass D.; Ukwaja K.N.; Thurston G.D.; Yun Jin K.; Simard, E.P.; Mills, E.; Park, E.K.; Catalá-López, F.; deVeber, G.; Gotay, C.; Khan, G.; Hosgood, H.D., III; Santos, I.S.; Leasher, J.L.; Singh, J.; Leigh, J.; Jonas, J.B.; Sanabria, J.; Beardsley, J.; Jacobsen, K.H.; Takahashi, K.; Franklin, R.C.; Ronfani, L.; Montico, M.; Naldi, L.; Tonelli, M.; Geleijnse, J.; Petzold, M.; Shrime, M.G.; Younis, M.; Yonemoto, N.; Breitborde, N.; Yip, P.; Pourmalek, F.; Lotufo, P.A.; Esteghamati, A.; Hankey, G.J.; Ali, R.; Lunevicius, R.; Malekzadeh, R.; Dellavalle, R.; Weintraub, R.; Lucas, R.; Hay, R.; Rojas-Rueda, D.; Westerman, R.; Sepanlou, S.G.; Nolte, S.; Patten, S.; Weichenthal, S.; Abera, S.F.; Fereshtehnejad, S.M.; Shiue, I.; Driscoll, T.; Vasankari, T.; Alsharif, U.; Rahimi-Movaghar, V.; Vlassov, V.V.; Marcenes, W.S.; Mekonnen, W.; Melaku, Y.A.; Yano, Y.; Artaman, A.; Campos, I.; MacLachlan, J.; Mueller, U.; Kim, D.; Trillini, M.; Eshrati, B.; Williams, H.C.; Shibuya, K.; Dandona, R.; Murthy, K.; Cowie, B.; Amare, A.T.; Antonio, C.A.; Castañeda-Orjuela, C.; van Gool, C.H.; Violante, F.; Oh, I.H.; Deribe, K.; Soreide, K.; Knibbs, L.; Kereselidze, M.; Green, M.; Cardenas, R.; Roy, N.; Tillmann, T.; Li, Y.; Krueger, H.; Monasta, L.; Dey, S.; Sheikhbahaei, S.; Hafezi-Nejad, N.; Kumar, G.A.; Sreeramareddy, C.T.; Dandona, L.; Wang, H.; Vollset, S.E.; Mokdad, A.; Salomon, J.A.; Lozano, R.; Vos, T.; Forouzanfar, M.; Lopez, A.; Murray, C.; Naghavi, M. Global Burden of Disease Cancer Collaboration. The global burden of cancer 2013. JAMA Oncol 2015,1(4),505-527 2. Soga S.; Akinaga S.; Shiotsu Y.; Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Curr Pharm Des 2013,19(3),366-376 3. Nakashima T.; Ishii T.; Tagaya H.; Seike T.; Nakagawa H.; Kanda Y.; Akinaga S.; Soga S.; Shiotsu Y.; New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res 2010,16(10),2792-2802 4. Ishii T.; Seike T.; Nakashima T.; Juliger S.; Maharaj L.; Soga S.; Akinaga S.; Cavenagh J.; Joel S.; Shiotsu Y.; Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib. Blood Cancer J 2012,2(4) 5. Supko J.G.; Hickman R.L.; Grever M.R.; Malspeis L.; Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother Pharmacol 1995,36(4),305-315
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|