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Title: | PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells |
Authors: | Wang, Yufeng Kuramitsu, Yasuhiro Baron, Byron Kitagawa, Takao Tokuda, Kazuhiro Akada, Junko Maehara, Shin-Ichiro Maehara, Yoshihiko Nakamura, Kazuyuki |
Keywords: | Pancreas -- Cancer Phosphorylation Cell therapy Stem cell factor |
Issue Date: | 2017 |
Publisher: | Spandidos Publications |
Citation: | Wang, Y., Kuramitsu, Y., Baron, B., Kitagawa, T., Tokuda, K., Akada, J., ... & Nakamura, K. (2017). PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells. International Journal of Oncology, 50(2), 606-612. |
Abstract: | LY294002 and wortmannin are chemical compounds that act as potent inhibitors of phosphoinositide 3-kinases (PI3Ks). Both of them are generally used to inhibit cell proliferation as cancer treatment by inhibiting the PI3K/ protein kinase B (AKT) signaling pathway. In this study, LY294002 (but not wortmannin) showed an abnormal ability to enhance AKT phosphorylation (at Ser472) specifically in gemcitabine (GEM)-resistant pancreatic cancer (PC) cell lines PK59 and KLM1-R. LY294002 was shown to activate AKT and accumulate phospho-AKT at the intracellular membrane in PK59, which was abolished by treatment with AKTi-1/2 or wortmannin. Inhibiting AKT phosphorylation by treatment with AKTi-1/2 or wortmannin further enhanced LY294002-induced cell death in PK59 and KLM1-R cells. In addition, treatment with wortmannin alone failed to inhibit cell proliferation in both PK59 and KLM1-R cells. Thus, our results reveal that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/99112 |
Appears in Collections: | Scholarly Works - CenMMB |
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