Related Experiment Video
Updated: Sep 17, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
PIMREG modulation of PI3K/Akt pathway enhances sorafenib resistance in Huh7 cells
Lei Zhang1, Aijun Gao1, Kaiyun Peng2
1Department of Medical Laboratory Technology, Medical College, Yangzhou Polytechnic College, Yangzhou 225009, China.
Background And Study Aims:
Sorafenib, as a novel multi-targeted oral tumor chemotherapeutic drug, has been found to exert an impact on the inhibition of cancer growth. Phosphatidylinositol-binding reticulin assembly protein interacting with mitotic regulatory factors (PIMREG) is strongly associated with oncology to drug resistance. However, how PIMREG modulates therapy tolerance to sorafenib in HCC and its potential regulatory mechanisms remain unclear. This study is abouta mechanistic approach to examine the action and mechanism of PIMREG in HCC-mediated sorafenib resistance.
Material And Methods:
The human hepatocellular carcinoma sensitive cell line Huh7 and drug-resistant cell line Huh7/SFB were used for the study, and different rates of PIMREG expansion in both cells were detected. Next, the study transfected PIMREG overexpression and interference vector into hepatoma cell line Huh7/SFB, and acted on the cells with solafenib exhibiting a concentration gradient. The growth inhibition rate and IC50 value of cells were detected by MTT method to determine the concentration and time of drug addition. Then, this study employed MTT, qRT-PCR, flow cytometry, and Western blot to assay the growth of these cells, which were induced through overexpression and disruption of PIMREG, in combination with sorafenib. The study also constructed an in vivo mouse tire sample test in order to investigate the influence of PIMREG upon the in vitro efficacy of sorafenib. In addition, the study used LY294002 inhibitors to explore the molecular mechanisms of PIMREG-mediated resistance to sorafenib in Huh7/SFB cells.
Results:
The expression level of PIMREG in cells of the Huh7/SFB resistant strain was clearly higher than that in cells of the sensitive strain Huh7. After transfection of sh-PIMREG, the IC50 value decreased significantly, while OE-PIMREG significantly increased the IC50 value of sorafinib. Compared with the control group, inhibition of cell proliferation by sorafenib was enhanced after interference with PIMREG, while the effect of overexpression of PIMREG was on the contrary. The efficacy of sorafenib was enhanced by knockout of PIMREG in living organisms. In addition, the PI3K/AKT signal pathway was necessary for PIMREG-induced sorafenib resistance. Subsequently, PIMREG regulated sorafenib-induced inhibition of the PI3K/AKT signaling pathway, and LY294002 blocked the signal pathway to reduce PIMREG-induced resistance.
Conclusion:
All in all, an increase in HCC resistance to sorafenib via the PIMREG-mediated PI3K/AKT pathway suggests that PIMREG is a key tumor-associated gene with significant implications for sorafenib resistance in tumor cells.
Insights
Phosphatidylinositol-binding reticulin assembly protein interacting with mitotic regulatory factors (PIMREG) drives sorafenib resistance in hepatocellular carcinoma (HCC). Targeting PIMREG enhances sorafenib efficacy by inhibiting the PI3K/AKT pathway, offering a potential therapeutic strategy for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Sorafenib is a multi-targeted oral chemotherapeutic agent used to inhibit cancer growth.
- Phosphatidylinositol-binding reticulin assembly protein interacting with mitotic regulatory factors (PIMREG) is linked to cancer drug resistance.
- The precise role and regulatory mechanisms of PIMREG in sorafenib resistance in hepatocellular carcinoma (HCC) remain largely undefined.
Purpose of the Study:
- To investigate the role of PIMREG in mediating sorafenib resistance in HCC.
- To elucidate the molecular mechanisms by which PIMREG influences HCC cell response to sorafenib therapy.
- To explore PIMREG as a potential therapeutic target for overcoming sorafenib resistance in HCC.
Main Methods:
- Utilized human HCC cell lines (Huh7 and Huh7/SFB) with varying sorafenib sensitivity.
- Manipulated PIMREG expression (overexpression and interference) in HCC cells and treated with sorafenib.
- Assessed cell viability, IC50 values, proliferation, and apoptosis using MTT, qRT-PCR, flow cytometry, and Western blot.
- Conducted in vivo mouse studies and utilized PI3K/AKT pathway inhibitors (LY294002) to explore mechanisms.
Main Results:
- PIMREG expression was significantly higher in sorafenib-resistant HCC cells (Huh7/SFB) compared to sensitive cells (Huh7).
- PIMREG interference decreased IC50 values and enhanced sorafenib's anti-proliferative effects, while PIMREG overexpression had the opposite effect.
- PIMREG knockout in vivo improved sorafenib efficacy.
- The PI3K/AKT signaling pathway was identified as crucial for PIMREG-mediated sorafenib resistance, with PIMREG regulating this pathway.
Conclusions:
- Elevated PIMREG expression confers resistance to sorafenib in HCC.
- PIMREG mediates sorafenib resistance through the PI3K/AKT signaling pathway.
- PIMREG represents a significant tumor-associated gene and a potential therapeutic target for enhancing sorafenib efficacy in HCC.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:20The JAK-STAT Signaling Pathway
02:23Abnormal Proliferation
02:34Inhibition of Cdk Activity