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.


Targeting PI3K/Akt/mTOR Pathway Identifies Differential Expression and Functional Role of IL8 in Liver Cancer Stem Cell Enrichment
Kahraman, Deniz Cansen; Atalay, Rengül (2019-11-01)
Activation of the PI3K/Akt/mTOR pathway is an important signaling mechanism involved in the development and the progression of liver cancer stem cell (LCSC) population during acquired Sorafenib resistance in advanced hepatocellular carcinoma (HCC). Therefore, identification of novel therapeutic targets involving this pathway and acting on LCSCs is highly essential. Here, we analyzed the bioactivities and the molecular pathways involved in the action of small-molecule PI3K/Akt/mTOR pathway inhibitors in comp...
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...
Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies
Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride (2016-02-01)
Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simva...
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance
Kaplan, Esra; Gündüz, Ufuk (2012-02-01)
Purpose: Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer. Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to...
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: