Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma

Liao, Junbin; Jin, Huilin; Li, Shaoqiang; Xu, Lixia; Peng, Zhenwei; Wei, Guohong; Long, Jianting; Guo, Yu; Zhou, Qi; Peng, Sui

doi:10.1186/s13046-019-1419-1

Cited by 44 publications

(42 citation statements)

References 47 publications

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“…Another research demonstrates that radiation could promote cancer cell survival through activating the PI3K/AKT pathway. 39 Our results showed overexpression of RAGE intensively activated PI3K/AKT in both SiHa and CaSki cells and knockdown of RAGE inhibited PI3K/AKT phosphorylation in SiHa cells. To further analyze the role of PI3K/AKT signaling pathway on RAGEmediated proliferation and apoptosis in cervical squamous cancer cells, PI3K/AKT specific inhibitor LY294002 was applied.…”

Section: Discussionsupporting

confidence: 49%

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

Li¹,

Song²,

Zhou³

et al. 2020

OTT

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Aim: The receptor for advanced glycation endproducts (RAGE) expression has been reported to be implicated with cancer development. In this study, the role of RAGE in the regulation of cervical squamous cancer cell proliferation, apoptosis and the mechanism of RAGE involved in the biological behaviors were explored. Methods: The RAGE expression was overexpressed or downregulated by lentivirus transfection. The effect of RAGE expression on cell proliferation was explored by CCK-8, MTT, and BrdU assay, and the effect of RAGE on tumor development was confirmed by the xenograft mouse model along with the immunohistochemistry stain of proliferating cell nuclear antigen (PCNA). Apoptosis was investigated by flow cytometry and TUNEL assay. Western blotting was performed to investigate the expression of possible proteins, including Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT. Results: Overexpression of RAGE promoted proliferation of cervical squamous cancer cell and increased PCNA expression. In the meantime, RAGE overexpression inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. The in vivo results showed that overexpression of RAGE enhanced tumor growth. Conversely, knockdown of RAGE exhibited opposed effects on cervical cancer cells and xenograft mouse model. Furthermore, RAGE inhibitor FPS-ZM1 effectively inhibited SiHa cell viability and PCNA expression, and increased cell apoptosis and Bax/Bcl-2 ratio. Moreover, PI3K inhibitor LY294002 effectively inhibited activation of PI3K and AKT, and further repressed RAGE overexpression-induced cell proliferation and apoptosis inhibition. Conclusion: RAGE promotes the growth ability of cervical squamous cell carcinoma by inducing PCNA expression and inhibiting cell apoptosis via inactivation of the PI3K/AKT pathway.

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Section: Discussionsupporting

confidence: 49%

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

Li¹,

Song²,

Zhou³

et al. 2020

OTT

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“…The phase III clinical study conducted by Li et al [ 12 ] (registration number: NCT01512745) showed that, in patients with advanced gastric cancer or adenocarcinoma of the gastroesophageal junction that failed second-line standard chemotherapy or above, the median OS and median PFS of the Apatinib group were both significantly longer than those of the placebo group (6.5 months vs. 4.7 months, HR: 0.709, 95% CI: 0.537–0.937, P =0.0149; 2.6 months vs. 1.8 months, HR: 0.444, 95% CI: 0.331–0.595, P <0.001, respectively). Moreover, Apatinib showed good efficacy and safety in the treatment of various tumors such as lung cancer [ 13 ], liver cancer [ 14 ], and breast cancer [ 15 ]. However, Apatinib has been rarely used in esophageal cancer treatment, especially esophageal squamous cell carcinoma, and there is a lack of medical evidence about whether Apatinib can improve the efficacy of concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma

Kong

Meng

et al. 2020

Med Sci Monit

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Background Esophageal cancer is a common gastrointestinal malignancy in China. We evaluated the efficacy and safety of adding Apatinib to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Material/Methods In this single-center retrospective study, we compared short-term efficacy, long-term efficacy, and adverse events between patients who received Apatinib and concurrent chemoradiotherapy (Apatinib group), and those who received only concurrent chemoradiotherapy (CCRT group). Results Sixty-five patients with stage II and III esophageal squamous cell carcinoma were enrolled (31 in the Apatinib group, 34 in the CCRT group). After treatment, the therapy response rate (the sum of the complete and partial remission rates) was significantly higher in the Apatinib group than in the CCRT group ( P =0.045); the complete remission rate was particularly higher in the Apatinib group. Median progression-free survival in the Apatinib group (12 months) was higher than that of the CCRT group (7 months), and the 1- and 2-year progression-free survival rates were significantly higher in the Apatinib group than in the CCRT group (47.0% vs. 30.3% and 20.2% vs. 12.1%, respectively; P =0.040). The main adverse effects of Apatinib treatment were elevated blood pressure, proteinuria, hand-foot syndrome, fatigue, and oral mucositis, all of which were level 1–2. Cox multivariate regression analysis indicated T stage and short-term efficacy were independent prognostic factors for overall and progression-free survival. Conclusions For patients with locally advanced esophageal squamous cell carcinoma, combining Apatinib with concurrent chemoradiotherapy can improve patient survival and significantly prolong progression-free survival, with tolerable adverse reactions.

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“…Notably, Sox9 expressing cells differentially upregulated genes were signi cantly enriched in the PI3K/AKT signaling pathway. Previous studies have shown that repressed PI3K/AKT signaling pathway predisposed cells to reduced DNA repair capacity, resulting in an increase of radiationinduced apoptosis (Liao et al, 2019). Consistent with a radio-resistant phenotype, another study demonstrated that PI3K/AKT dependent pathways play a protective or promoting regenerative role after radiation injury (Yang et al, 2014).…”

Section: Discussionmentioning

confidence: 89%

Sox9-expressing cells promote regeneration after radiation-induced lung injury via PI3K/AKT pathway

Chen

Zhong

et al. 2021

Preprint

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Background Radiation induced lung injury (RILI) is considered as one of the most common complications of thoracic radiation. Recent studies have focused on stem cells properties to obtain ideal therapeutic effects and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remain unknown. Methods We successfully obtain SOX9CreER, RosatdTomato and RosaDTA mice and identify Sox9-expressing cells through lineage tracing assay. Then we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9 expressing cells during lung regeneration via an online single cell RNA-seq dataset. Results In our study, we demonstrated Sox9-expressing cells promote regenerative of lung tissues and ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of online scRNA-seq dataset revealed an enrichment of PI3K/AKT pathway in Sox9-expressing cells during lung epithelium regeneration. Finally, AKT inhibitor Perifosine could suppress the regenerative effects of Sox9-expressing cells. Conclusions Taken together, our study suggests that Sox9-expressing cells may serve as a therapeutic target in the setting of lung tissue after RILI.

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Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma

Cited by 44 publications

References 47 publications

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma

Sox9-expressing cells promote regeneration after radiation-induced lung injury via PI3K/AKT pathway

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