<i>ING4</i>expressing oncolytic vaccinia virus promotes anti-tumor efficiency and synergizes with gemcitabine in pancreatic cancer

Wu, Yafang; Mou, Xiaozhou; Wang, Shibing; Liu, Xinge; Sun, Xiaodong

doi:10.18632/oncotarget.21095

Cited by 14 publications

(12 citation statements)

References 44 publications

(54 reference statements)

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“…Our previous studies have demonstrated that oVV-ING4 indeed blocks cell cycle in G2 phase. 33 Despite cytarabine is an S-phase-specific chemotherapeutic drug, its synergistic anticancer effect with oVV-ING4 can be observed in Figure 5 . We speculate that this may be related to the complex action mechanism of cytarabine.…”

Section: Discussionmentioning

confidence: 99%

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Peng¹,

Wang²,

Fan³

et al. 2018

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BackgroundIn consideration of the drug resistance and side effects associated with cytarabine, one of the most effective drugs for the treatment of acute myeloid leukemia (AML), there is a need for safer and effective strategies.MethodsIn the present investigation, we fabricated a new oncolytic vaccinia virus (oVV-ING4), which expresses the inhibitor of growth family member 4 (ING4) and explored its antitumor activity individually and in combination with cytarabine in AML cells.ResultsThe experiments confirmed that oVV can efficiently and specifically infect leukemia cells, and augment the ING4 gene expression. Flow cytometry and western blot demonstrated that oVV-ING4 enhances apoptosis and G2/M phase arrest in AML cells, and causes remarkable cancer cell death. In addition, the synergistic efficiency of oVV-ING4 and cytarabine was investigated in vitro and in vivo; the combination significantly inhibited the survival of leukemia cells in vitro and xenografted KG-1 AML tumor growth in vivo.ConclusionIn brief, oVV-ING4 can increase the sensitivity of leukemia cells to cytarabine and induce cell apoptosis in vitro and in vivo. Thus, oVV-ING4 may be a promising therapeutic candidate for leukemia and in combination with cytarabine represents a potential antitumor therapy.

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Section: Discussionmentioning

confidence: 99%

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Peng¹,

Wang²,

Fan³

et al. 2018

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“…34 Recombinant VACV has shown therapeutic effects in several murine tumor models, including those of glioblastoma, pancreatic cancer, and melanoma. [35][36][37][38] Interestingly, we found that both WT and recombinant VACV were less replicative in the murine triple-negative breast cancer (TNBC) cell line 4T1, which shows high levels of TTP, 39 both in vitro and in vivo. Furthermore, TNBC cells from different species differ in terms of TTP expression, which affects the replication of recombinant VACV.…”

Section: Discussionmentioning

confidence: 95%

<p>The Ectopic Expression of SurvivinT34A and FilC Can Enhance the Oncolytic Effects of Vaccinia Virus in Murine Gastric Cancer</p>

Wang¹,

Luo²,

Sun³

et al. 2020

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Background/Aims: Anti-tumor vaccines have been shown to be effective in cancer therapeutics ever since the anti-HPV vaccine was developed. Compared to conventional chemotherapy, anti-tumor vaccines can specifically target cancer cells and they have lower side effects. We developed a recombinant vaccinia virus (VACV) (Western Reserve) WR strain, and we tested its anti-tumor effects in an animal model. Methods: A recombinant VACV WR strain expressing mutant survivin T34A (SurT34A) and FilC was constructed and validated. Its oncolytic effect was tested in vitro using a CCK-8 assay, and its tolerance and anti-tumor effects were tested in a murine gastric cancer model. The proportion of lymphocytes in the spleen and tumor was determined after antibody-mediated immuno-depletion. Results: The recombinant VACV showed a stronger replication ability in tumor cells, and it was safe in vivo, even at high doses. The combination of vv-SurT34A and vv-FilC resulted in a stronger anti-tumor effect compared to either construct alone. However, the inhibitory effect of vv-SurT34A was stronger than the combination. The recombinant VACV activated the host immune response, as indicated by lymphocyte infiltration in the spleen and tumor tissues. Conclusion: The recombinant VACV WR strain expressing SurT34A and FilC is a safe and effective anti-tumor vaccine.

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“…In addition, Smac is expressed at a lower level in pancreatic tumors (10 of 10) compared with normal pancreas (data not shown). Several clinical studies have reported synergistic antitumor activity of the co-treatment with oVV and chemotherapy or radiation therapy ( 30 , 31 ). Additionally, it has been suggested that the route of combination of oVV with cytotoxic chemotherapies is another factor in potentiating the effects of oVV and optimizing the therapy ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine combined with an engineered oncolytic vaccinia virus exhibits a synergistic suppressive effect on the tumor growth of pancreatic cancer

Chen

Fan

et al. 2018

Oncol Rep

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Pancreatic cancer (PC) is a lethal solid malignancy with resistance to traditional chemotherapy. Recently, considerable studies have demonstrated the ubiquitous antitumor properties of gene therapy mediated by the oncolytic vaccinia virus. The second mitochondrial-derived activator of caspase (Smac) has been identified as an innovative tumor suppressor that augments the chemosensitivity of cancer cells. However, the therapeutic value of oncolytic vaccinia virus (oVV)-mediated Smac gene transfer in pancreatic cancer is yet to be elucidated. In the present study, oncolytic vaccinia virus expressing Smac (second mitochondrial-derived activator of caspase) (oVV-Smac) was used to examine its beneficial value when used alone or with gemcitabine in pancreatic cancer in vitro and in vivo. The expression of Smac was evaluated by western blot analysis and quantitative polymerase chain reaction, oVV-Smac cytotoxicity by MTT assay, and apoptosis by flow cytometry and western blot analysis. Furthermore, the inhibitory effect of oVV-Smac combined with gemcitabine was also evaluated. The results indicated that oVV-Smac achieved high levels of Smac, greater cytotoxicity, and potentiated apoptosis. Moreover, co-treatment with oVV-Smac and gemcitabine resulted in a synergistic effect in vitro and in vivo. Therefore, our findings advance oVV-Smac as a potential therapeutic candidate in pancreatic cancer and indicated the synergistic effects of co-treatment with oVV-Smac and gemcitabine.

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ING4expressing oncolytic vaccinia virus promotes anti-tumor efficiency and synergizes with gemcitabine in pancreatic cancer

Cited by 14 publications

References 44 publications

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

<p>The Ectopic Expression of SurvivinT34A and FilC Can Enhance the Oncolytic Effects of Vaccinia Virus in Murine Gastric Cancer</p>

Gemcitabine combined with an engineered oncolytic vaccinia virus exhibits a synergistic suppressive effect on the tumor growth of pancreatic cancer

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