Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells.

Narci, Kubra
Kahraman, Deniz Cansen
Koyas, Altay
Ersahin, Tulin
Tuncbag, Nurcan
Atalay, Rengul Cetin
Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted therapies through synergistic activities, isoform specific effects of the inhibitors are usually ignored. This study concentrated on PI3K/Akt/mTOR pathway and the differential combinatory bioactivities of isoform specific PI3K-alpha inhibitor (PIK-75) or PI3K-beta inhibitor (TGX-221) with Sorafenib dependent on PTEN context.


Regulation of Glutathione S-Transferase Mu with type 1 diabetes and its regulation with antioxidants
SADİ, GÖKHAN; Kartal, Deniz Irtem; Güray, Nülüfer Tülün (2013-01-01)
Objective: Increased oxidative stress is now related with the pathogenesis and the chronic complications associated with the disease, diabetes mellitus. While roles of oxidative stress in diabetic complications are widely studied, the molecular mechanisms playing role in the regulations of detoxification enzymes in the presence of antioxidants have not been clearly established because of the complexity of the pathways.
Enantiomerically pure beta-dipeptide derivative induces anticancer activity against human hormone-refractory prostate cancer through both PI3K/Akt-dependent and -independent pathways
Chan, Mei-Ling; Yu, Chia-Chun; Hsu, Jui-Ling; Leu, Wohn-Jenn; Chan, She-Hung; Hsu, Lih-Ching; Liu, Shih-Ping; Ivantcova, Polina M.; Doğan, Özdemir; Braese, Stefan; KUDRYAVTSEV, Konstantin V; GUH, Jih Hwa (Impact Journals, LLC, 2017-11-14)
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure beta-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the ...
Reversal of multidrug resistance in mcf-7 breast adenocarcinoma cell line by silencing interleukin 6 with RNA interference
Çakmak, Neşe; Gündüz, Ufuk; Department of Biology (2013)
Multidrug resistance (MDR) in cancer is characterized by development of resistance to several unrelated drugs upon long time administration of a certain type of chemotherapeutic agent. In doxorubicin resistant MCF-7 cell line, resistance is developed mainly by upregulation of MDR1 gene which encodes an ABC transporter protein known as P-glycoprotein. Interleukin 6 (IL-6) is a cytokine which acts as a growth factor for certain cell types including some cancer cells. IL-6 is found at high levels in cancer pat...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Molecular investigation of therapeutical effects of Ɣ-tocotrienol conjugation therapy with doxorubicin on hepatocellular carcinoma cell line HePG2
Özyurt, İpek; Son, Çağdaş Devrim; Department of Biology (2017)
Hepatocellular carcinoma (HCC) is the fifth leading tumor of the liver tissue in terms of frequency of occurrence and third in terms of mortality. Even though, the most widely used chemotherapeutic agent doxorubicin in treatment of HCC had a great impact for development of therapeutic strategies preventing the progression of tumor formation and elucidating the physiological characteristics of tumor tissue. Moreover, use of doxorubicin minimizes the side effects of the drug in the individual and prevents the...
Citation Formats
K. Narci, D. C. Kahraman, A. Koyas, T. Ersahin, N. Tuncbag, and R. C. Atalay, “Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells.,” BMC cancer, vol. 22, no. 1, pp. 320–320, 2022, Accessed: 00, 2022. [Online]. Available: