NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

Objective: Radiation therapy, one of the major treatments for liver cancer, causes DNA damage and cell death. Since the liver cancer cells have a strong capacity to repair irradiative injury, new medicines to enhance this treatment are urgently required. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-dependent protein kinase (DNA-PK) in radiosensitization of hepatocellular carcinoma HepG2 cells. Methods: Cell Counting Kit-8 (CCK-8) was first used to evaluate the proliferation of HepG2 cells under NU7441 treatment. SDS-PAGE and Western blot were then performed to study the protein expression leading to the DNA damage repair. Further, neutral single cell gel electrophoresis and immunofluorescence assay were carried out to assess DNA repair. Finally, flow cytometry was implemented to examine the changes in cell cycle. Results: NU7441 reduced the CCK-8 counts in the HepG2 culture, further enhanced 60Coγ radiation injury to HepG2 cells, which was manifested by decreasing the DNA-PKcs (S2056) protein expression, increasing γH2AX foci number, prolonging the tail moment of the comet cells, and inducing cell cycle arrest at G2/M phase. Conclusion: NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer.

Download Full-text

Tumor Cells Talk to Normal Cells Through Exosomes to Rebuild the Tumor Microenvironment

10.21203/rs.3.rs-444267/v1 ◽

2021 ◽

Author(s):

Chunwen Pu ◽

Qi Wang ◽

Aijun Sun ◽

Ping Sun ◽

Hui Huang ◽

...

Keyword(s):

Cell Cycle ◽

Flow Cytometry ◽

Cell Proliferation ◽

Tumor Microenvironment ◽

Liver Cancer ◽

Cancer Cells ◽

Cell Invasion ◽

Hepg2 Cells ◽

Normal Cells ◽

Liver Cancer Cells

Abstract BackgroundExosomes play a key role in the growth of normal cells and various diseases such as cancer. Tumor exosomes regulate the connection between normal cells and cancer cells in the tumor microenvironment, thereby promoting the growth and invasion of cancer cells.MethodsWe used HepG2 cells silenced by shRNA targeting GPC3, LO2 and HepG2 cells treated with different concentrations of GPC3. We determined the effects of GPC3 on cell proliferation, apoptosis and invasion using CCK8, flow cytometry and Transwell, and Western blotting Method to determine the expression of GPC3/WNT3A/β-catenin.HepG2 exosomes (Exo) and HepG2 exosomes treated with shRNA targeting GPC3 (sh-GPC3-Exo) were used to treat LO2 and HepG2 cells separately. Cell proliferation was measured by CCK8 experiment.The cell cycle and apoptosis were measured by flow cytometry. The cell invasion ability was analyzed by Transwell. The expression of GPC3/WNT3A/β-catenin signal protein was determined by Western blotting.ResultsThis is the first study to prove the bidirectional regulation of GPC3 between normal cells and liver cancer cells. After treatment of LO2 cells and HepG2 cells with GPC3, the LO2 cell cycle was blocked in the G0/G1 phase, while inhibiting cell proliferation, promoting cell apoptosis and invasion, but for HepG2 cells it appeared to promote proliferation.Silencing GPC3 can inhibit the proliferation and invasion, and promote cell apoptosis of HepG2. Subsequent experiments found that the expression of GPC3 was found in both LO2 and HepG2 exosomes, and the expression of GPC3 in HepG2 exosomes was significantly higher than that in LO2 exosomes. These suggest that GPC3 in exosomes has the potential to become a biomarker of HCC.In addition, HepG2 exosomes (Exo) can inhibit the proliferation of LO2 cells and promote apoptosis and invasion, which is consistent with the effect of GPC3 treatment. We also found that GPC3 is contained in HepG2 exosomes (shGPC3-Exo) that have silenced GPC3, which has the same effect on LO2 cells as HepG2 exosomes (Exo), but the degree of influence is reduced. shGPC3-Exo showed a promoting effect on the proliferation of HepG2 cells, but inhibited cell invasion. Therefore, GPC3 in Exo plays a role in the proliferation of LO2 cells and HepG2 cells. Further studies have shown that GPC3 in liver cancer exosomes regulates the proliferation, apoptosis and invasion of LO2 and HepG2 cells through the Wnt /β-catenin signaling pathway.ConclusionGPC3 in the exosomes of liver cancer cells inhibits the proliferation of normal liver cells and promotes apoptosis by activating the Wnt/β-catenin signaling pathway, promotes the proliferation of liver cancer cells, and assists the occurrence and development of HCC.

Download Full-text

Echinacoside exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer

Cancer Cell International ◽

10.1186/s12935-021-01890-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen Li ◽

Jing Zhou ◽

Yajie Zhang ◽

Jing Zhang ◽

Xue Li ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Hepg2 Cells ◽

Luciferase Reporter ◽

Therapeutic Effects ◽

Dependent Manner ◽

Expression Levels ◽

Liver Cancer Cells ◽

Anti Tumor Activity ◽

Tgf Β1

Abstract Background Echinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. However, the effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells. Methods Two types of liver cancer cells Huh7 and HepG2 were treated with different doses of ECH at different times and gradients. MTT and colony formation assays were used to determine the effects of ECH on the viability of Huh7 and HepG2 cells. Transwell assays and flow cytometry assays were used to detect the effects of ECH treatment on the invasion, migration, apoptosis and cell cycle of Huh7 and HepG2 cells. Western blot analysis was used to detect the effects of ECH on the expression levels of TGF-β1, smad3, smad7, apoptosis-related proteins (Caspase-3, Caspase-8), and Cyto C in liver cancer cells. The relationship between miR-503-3p and TGF-β1 was detected using bioinformatics analysis and Luciferase reporter assay. Results The results showed that ECH inhibited the proliferation, invasion and migration of Huh7 and HepG2 cells in a dose- and time-dependent manner. Moreover, we found that ECH caused Huh7 and HepG2 cell apoptosis by blocking cells in S phase. Furthermore, the expression of miR-503-3p was found to be reduced in liver tumor tissues, but ECH treatment increased the expression of miR-503-3p in Huh7 and HepG2 cells. In addition, we found that TGF-β1 was identified as a potential target of miR-503-3p. ECH promoted the activation of the TGF-β1/Smad signaling pathway and increased the expression levels of Bax/Bcl-2. Moreover, ECH could trigger the release of mitochondrial Cyto C, and cause the reaction Caspases grade. Conclusions This study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer.

Download Full-text

A resveratrol analog, phoyunbene B, induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2011.12.095 ◽

2012 ◽

Vol 22 (5) ◽

pp. 2114-2118 ◽

Cited By ~ 17

Author(s):

Guanghui Wang ◽

Xiaoyu Guo ◽

Haifeng Chen ◽

Ting Lin ◽

Yang Xu ◽

...

Keyword(s):

Cell Cycle ◽

Liver Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

M Cell ◽

Liver Cancer Cells ◽

Cycle Arrest

Download Full-text

Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells

Cancer Letters ◽

10.1016/j.canlet.2005.10.050 ◽

2006 ◽

Vol 241 (1) ◽

pp. 102-109 ◽

Cited By ~ 55

Author(s):

Guanghui Wang ◽

Haifeng Chen ◽

Minghui Huang ◽

Naili Wang ◽

Jinchao Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Liver Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

M Cell ◽

Liver Cancer Cells ◽

Cycle Arrest

Download Full-text

Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: Implications for the role of Zbtb7 in cell cycle regulation

Molecular Medicine Reports ◽

10.3892/mmr.2012.846 ◽

2012 ◽

Author(s):

Yuyang Jiang

Keyword(s):

Cell Cycle ◽

Liver Cancer ◽

Cancer Cells ◽

Cell Cycle Regulation ◽

Liver Cancer Cells ◽

Cycle Regulation

Download Full-text

Histone deacetylase inhibitor MGCD0103 causes cell cycle arrest, apoptosis, and autophagy in liver cancer cells

Journal of Cancer ◽

10.7150/jca.34091 ◽

2020 ◽

Vol 11 (7) ◽

pp. 1915-1926 ◽

Cited By ~ 2

Author(s):

Bo Liao ◽

Quan Sun ◽

Yufeng Yuan ◽

Yuchun Yin ◽

Jianguo Qiao ◽

...

Keyword(s):

Cell Cycle ◽

Liver Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Liver Cancer Cells ◽

Cycle Arrest ◽

Deacetylase Inhibitor

Download Full-text

Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

International Journal of Molecular Sciences ◽

10.3390/ijms21186684 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6684

Author(s):

Samuele Lodovichi ◽

Tiziana Cervelli ◽

Achille Pellicioli ◽

Alvaro Galli

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Repair ◽

Cancer Therapy ◽

Clinical Outcome ◽

Cancer Cells ◽

Cell Cycle Checkpoint ◽

Normal Cells ◽

Cycle Checkpoint ◽

Repair Pathways

Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.

Download Full-text