The Sineoculis Homeobox Homolog 1 (SIX1) Gene Regulates Paclitaxel Resistance by Affecting Reactive Oxygen Species and Autophagy in Human Hepatocellular Carcinoma Cell Line HepG2

Li, Baowei; Zhao, Shahe; Geng, Ruipeng; Huo, Zhongchao; Zhang, Hui

doi:10.12659/msm.906361

Cited by 11 publications

(3 citation statements)

References 33 publications

(28 reference statements)

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“…25 SIX1 may increase resistance to chemotherapy in liver cancer. 16,26 Under hypoxic conditions, PIM1 is upregulated, resulting in increased glucose uptake and facilitated glycolysis, which promotes tumor progression and metastasis. 19 Downregulation of PIM1 suppressed tumor growth in HCC cells.…”

Section: Expression Of Genes Associated With the Warburg Effectmentioning

confidence: 99%

<p>Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells</p>

Zhang¹,

Guo²,

Kaboli³

et al. 2020

OTT

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The Warburg effect, also known as aerobic glycolysis, plays a dominant role in the development of gastrointestinal (GI) cancers. In this study, we analyzed the expression of key genes involved in the Warburg effect in GI cancers and investigated the effect of suppressing the Warburg effect in vitro in liver cancer cell lines. Methods: The Cancer Genome Atlas (TCGA) RNA-Seq data were used to determine gene expression levels, which were analyzed with GraphPad Prism 7.00. Genetic alterations were queried with cBioPortal. The influence of the Warburg effect on liver cancer cell viability, migration and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined by means of MTT, transwell and GAPDH activity assays. Results: The levels of expression of genes associated with the Warburg effect were increased in tumors. To our knowledge, this is the first report of upregulated expression of CUEDC2, HMGB2, PFKFB4, PFKP and SIX1 in liver cancer. Clinically, overexpression of these genes was associated with significantly worse overall survival of liver cancer patients. In vitro, selective inhibition of GADPH suppressed the growth and metastasis of Huh-7, Bel7404 and Hep3B hepatocellular carcinoma cell lines. Conclusion: The Warburg effect may play an important role in GI cancers, especially in liver cancer.

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Section: Expression Of Genes Associated With the Warburg Effectmentioning

confidence: 99%

<p>Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells</p>

Zhang¹,

Guo²,

Kaboli³

et al. 2020

OTT

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“…The use of microtubule-directed agent is an alternative with a high therapeutic potential in HCC. However, the multidrug resistance (MDR) phenomenon, which is acquired after exposure to a chemotherapeutic agent, including PTX, has become a major obstacle in the treatment of HCC [3,4,5,6,7]. Various mechanisms have been attributed to MDR, such as increased drug outflow, increased repair of DNA damage, reduced apoptosis, and/or altered drug metabolism [8].…”

Section: Introductionmentioning

confidence: 99%

Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

et al. 2019

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Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant Artemisia ludovisiana, to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin.

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“…Therefore, for most cases of HCC, chemotherapy is the main treatment strategy (Nagano, 2010). However, hepatoma cells are known to be highly resistant to chemotherapeutic drugs, including paclitaxel (Wu et al, 2018; Lin et al, 2018a; Huang et al, 2018; Li et al, 2018). Chemoresistance has become a major obstacle in the treatment of HCC, clarifying the molecular mechanisms of drug resistance in HCC is important for developing more effective therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Lin28B is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

Tian

Shangguan

Zhou

et al. 2018

Preprint

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statement upregulation of Lin28B not only confers poor prognosis in HCC patients but also increases chemoresistance in HCC cells. Thus, Lin28B may serve as a predictive biomarker for use to reverse chemoresistance in clinical practice. AbstractChemoresistance remains a big challenge in hepatocellular carcinoma (HCC) treatment. Several studies indicated that RNA-binding protein Lin28B serves an oncogenic role in HCC, but its activity in HCC chemotherapy has never been assessed. In this study, we found that overexpression of Lin28B significantly increased the paclitaxel chemoresistance in two different HCC cells lines while silencing Lin28B reduced the chemoresistance in paclitaxel-resistance HCC cells. Curcumin, a natural anti-cancer agent, increased the sensitivity of HCC cells to paclitaxel through inhibiting NF-κB stimulated Lin28B expression both in vitro and in vivo. Furthermore, by analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) and GSE14520 databases, we found that Lin28B was highly up-regulated in HCC tissue compared with that in normal tissue and associated with -fetoprotein levels, and that patients with Lin28B higher expression had a significant shorter overall survival time than those with Lin28B lower expression. Our data reveal that Lin28B may serve as a predictive biomarker and a treatment target to reverse HCC chemotherapy resistance in future clinical practice.

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The Sineoculis Homeobox Homolog 1 (SIX1) Gene Regulates Paclitaxel Resistance by Affecting Reactive Oxygen Species and Autophagy in Human Hepatocellular Carcinoma Cell Line HepG2

Cited by 11 publications

References 33 publications

<p>Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells</p>

<p>Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells</p>

Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

Lin28B is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

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