Combination of DESI2 and endostatin gene therapy significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis

Yan, Huaying; Guo, Wenhao; Li, Ké; Tang, Ming; Zhao, Xinyu; Lei, Yi; Nie, Chao; Zhu, Yong‐Guan

doi:10.1016/j.yexcr.2018.07.040

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…Among RPs, human ribosomal protein S7 (RPS7) is receiving increasing attention for its different functions in multiple cancers. RPS7 functions as a tumor suppressor in colorectal cancer and ovarian tumors, whereas it acts as a pro-oncogenic factor in prostate cancer, lung adenocarcinoma and breast cancer [ 11 – 15 ]. Nonetheless, the role of RPS7 in the occurrence and development of HCC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling

Zhou,

Yang,

et al. 2024

J Exp Clin Cancer Res

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Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

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Section: Introductionmentioning

confidence: 99%

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling

Zhou,

Yang,

et al. 2024

J Exp Clin Cancer Res

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“… 15 – 17 (2) Endostar has the ability to improve radiation sensitivity in tumor tissue by inducing apoptosis in tumor cells and disrupting the tumor cell cycle during the radiation sensitive phase. 14 , 18 – 20 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety Analysis of Recombinant Human Endostatin (Endostar) Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer: A 2-Center Retrospective Study

Feng,

Li,

Sun

et al. 2024

Technol Cancer Res Treat

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Background This study aims to assess the efficacy and safety of Endostar in the management of locally advanced cervical cancer. Methods This retrospective, 2-center study enrolled 41 patients with locally advanced cervical cancer between June 2017 and December 2020. The patients were subjected to a combination of Endostar and chemoradiotherapy until they experienced disease progression or an unacceptable level of toxicity. The patients in the Endostar combined chemoradiotherapy (E + CRT) and CRT groups were matched 1:1 based on clinical features, including age, disease stage, and pathological type. The therapeutic efficacy and safety outcomes were compared between the 2 groups. Results Early treatment response: the CR rates in E + CRT and CRT groups were 48.8% and 26.8%, respectively ( χ2 = 4.20, P < .05). The ORR and DCR were not significantly different between the 2 groups. Long-term efficacy: there was no significant difference in the 1-year and 2-year PFS rates and OS rates between 2 groups. However, in patients with stage IIB, subgroup analyses revealed a significant difference in PFS between the 2 groups ( P < .05). Prognostic factors: stage, Eastern Cooperative Oncology Group (ECOG) score, and tumor size were independent predictive factors for PFS, while ECOG score and tumor size were those of OS in patients with locally advanced cervical cancer. Safety: The incidence of grade III-IV myelosuppression was significantly lower in E + CRT group than in CRT group ( P < .05). Conclusions The combination of Endostar and concurrent CRT exhibited greater efficacy in treating locally advanced cervical cancer with no severe adverse reactions, when compared to simple CRT. It is expected that this approach will evolve into a new treatment alternative for patients with locally advanced cervical cancer.

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“…Additionally, studies have shown that when exposed to radiation, epidermal growth factor receptor (EGFR) translocates to the nucleus to regulate DNA-PKcs activity and promote double-strand break repair [23], and that VEGF influences radiation-induced changes in EGFR subcellular localization [24]. Endostatin was found to promote DNA damage in colon cancer cells by interacting with DNA-PKcs [25]. Additionally, by inhibiting the DNA-PKcs signaling pathway, bevacizumab was found to improve the radiotherapy sensitivity of non-small cell lung cancer cells [26].…”

Section: Discussionmentioning

confidence: 99%

Endostar Synergizes with Radiotherapy to Inhibit Angiogenesis of Cervical Cancer in a Subcutaneous Xenograft Mouse Model

Xu¹,

Zhao²,

Hu³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: To investigate the synergic effect and underlying mechanism of Endostar, a recombinant human endostatin used for antiangiogenesis, in radiotherapy for cervical cancer. Methods: The Cell Counting Kit-8 (CCK-8) assay and plate cloning experiment were first employed to analyze the proliferation of HeLa and SiHa cervical cancer cells and human umbilical vein vascular endothelial cells (HUVECs). Flow cytometry was used to detect apoptosis and cell cycle progression. A tube formation assay was used to assess angiogenesis in vitro. The expression of gamma H2A histone family member X (γ-H2AX) and activation of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were detected by immunofluorescence and western blotting, respectively. In a HeLa xenograft model, tumor tissue expression of CD31 and alpha smooth muscle actin and serum expression of VEGF-A were detected by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay, respectively. Results: The CCK-8 and plate cloning assays showed that Endostar and radiotherapy synergistically inhibited the growth of HUVECs but not HeLa and SiHa cells. The flow cytometric results showed that Endostar only promoted radiotherapy-induced apoptosis and G2/M phase arrest in HUVECs (p < 0.05). Endostar combined with radiotherapy also significantly inhibited tube formation by HUVECs (p < 0.05). Furthermore, Endostar inhibited the radiotherapy-induced expression of γH2AX (p < 0.05) and phosphorylation of VEGFR2/PI3K/AKT/DNA-PK in HUVECs (p < 0.05). IHC showed that Endostar enhanced the inhibitory effect of radiotherapy on the microvessel density in xenograft tumor tissues (p < 0.05), as well as serum VEGF-A expression (p < 0.05). The tumor volume in the combination therapy groups (1200 mm 3 ) was significantly lower than in the control group (2500 mm 3 ; p < 0.05). Conclusions: Our findings provide experimental evidence and a theoretical basis for the application of Endostar in combination with irradiation for anti-cervical cancer treatment.

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Combination of DESI2 and endostatin gene therapy significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis

Cited by 8 publications

References 37 publications

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling

Efficacy and Safety Analysis of Recombinant Human Endostatin (Endostar) Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer: A 2-Center Retrospective Study

Endostar Synergizes with Radiotherapy to Inhibit Angiogenesis of Cervical Cancer in a Subcutaneous Xenograft Mouse Model

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