Inhibitory effect of Survivin promoter-regulated oncolytic adenovirus carrying P53 gene against gallbladder cancer

Gastric cancer (GC) is one of the major causes of cancer related mortality. The use of oncolytic virus for cancer gene-virotherapy is a new approach for the treatment of human cancers. In this study, a novel Survivin promoter driven recombinant oncolytic adenovirus carrying mK5 or MnSOD gene was constructed, which was modified after deletion of E1B gene. Human plasminogen Kringle 5 mutant ( mK5 ) and manganese superoxide dismutase ( MnSOD ) are both potential tumor suppressor genes. To construct Ad-Surp- mK5 and Ad-Surp- MnSOD oncolytic adenovirus, we hypothesized that the combination of the two viruses would enhance the therapeutic efficacy of GC as compared to the virus alone. The results of the in vitro experiments revealed that the combination of adenovirus carrying mK5 and MnSOD gene exhibited stronger cytotoxicity to GC cell lines as compared to the virus alone, Additionally, the virus could selectively kill cancer cells and human somatic cells. Cell staining, flow cytometry and western blot analysis showed that the combination of two adenovirus containing therapeutic genes could promote the apoptosis of cancer cells. In vivo experiments further verified that Ad-Surp- mK5 in combination with Ad-Surp- MnSOD exhibited significant inhibitory effect on the growth of GC tumor xenograft as compared to the virus alone, and no significant difference was observed in the body weight of treatment and the normal mice. In conclusion, the combination of our two newly constructed recombinant oncolytic adenovirus containing mK5 or MnSOD therapeutic genes could significantly inhibit gastric cancer growth by inducing apoptosis, suggestive of its potential for GC therapy.

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Combined oncolytic adenovirus carrying MnSOD and mK5 genes both regulated by survivin promoter has a synergistic inhibitory effect on gastric cancer

Neoplasma ◽

10.4149/neo_2021_210508n624 ◽

2021 ◽

Author(s):

Shan-Shan Liu ◽

Jin-Qing Hu ◽

Jin-Fa Gu ◽

Ai-Min Ni ◽

Wen-Hao Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Inhibitory Effect ◽

Oncolytic Adenovirus ◽

Survivin Promoter ◽

Synergistic Inhibitory Effect

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Betulinic acid induces apoptosis of gallbladder cancer cells via repressing SCD1

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz148 ◽

2020 ◽

Vol 52 (2) ◽

pp. 200-206 ◽

Cited By ~ 2

Author(s):

Hongfei Wang ◽

Fangxiao Dong ◽

Ye Wang ◽

Xu’an Wang ◽

Defei Hong ◽

...

Keyword(s):

Gallbladder Cancer ◽

Betulinic Acid ◽

Polymerase Chain Reaction Analysis ◽

Inhibitory Effect ◽

Dependent Manner ◽

Antitumor Effects ◽

Concentration Dependent Manner ◽

Polymerase Chain ◽

Induced Apoptosis ◽

Scd1 Expression

Abstract Gallbladder cancer (GBC) is the most common and aggressive malignancy of the biliary tract. Betulinic acid (BetA) has been reported to have anti-inflammatory and antitumor effects; however, the effect of BetA on GBC is still unknown. In this study, we investigated the effect of BetA on five GBC cell lines and found that BetA significantly inhibited the proliferation of NOZ cells but had little inhibitory effect on other GBC cells. BetA disturbed mitochondrial membrane potential and induced apoptosis in NOZ cells. Real-time polymerase chain reaction analysis revealed that stearoyl-coenzyme A desaturase 1 (SCD1) was highly expressed in NOZ cells but low expressed in other GBC cells. BetA inhibited SCD1 expression in a concentration-dependent manner in NOZ cells. Downregulation of SCD1 expression by RNA interference inhibited the proliferation of NOZ cells and induced cell apoptosis. Moreover, BetA inhibited the growth of xenografted tumors and suppressed SCD1 expression in nude mice. Thus, our results showed that BetA induced apoptosis through repressing SCD1 expression in GBC, suggesting that BetA might be an effective agent for the treatment of patients with GBC that highly expresses SCD1.

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Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone

Journal of Endocrinology ◽

10.1677/joe.0.1790055 ◽

2003 ◽

Vol 179 (1) ◽

pp. 55-62 ◽

Cited By ~ 25

Author(s):

M Alkhalaf ◽

AM El-Mowafy

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Growth Inhibition ◽

Cancer Cells ◽

Breast Cancer Cells ◽

P53 Protein ◽

P53 Gene ◽

Inhibitory Effect ◽

Antiproliferative Effect ◽

Mcf 7

We have recently shown that growth inhibition of breast cancer cells by progesterone is due to the induction of cell differentiation, but not apoptosis. Because the tumor suppressor protein p53 plays a central role in normal cell growth and in tumor suppression, we have examined the effect of progesterone on the levels of this protein in MCF-7 cells. We show here that the antiproliferative effect of progesterone is accompanied with down-regulation of endogenous p53 protein. To study the effect of progesterone on cell growth in the presence of normal levels of p53 protein, we used transient transfection to overexpress p53 protein. MCF-7 cells were transfected with a p53 expressing vector that contains p53 human cDNA under the control of a cytomegalovirus promoter. Cell growth, cell viability, and apoptosis were analyzed in the transfected cells after six days of exposure to 100 nM progesterone. We show here that progesterone significantly enhances growth inhibition and apoptosis in MCF-7 cells overexpressing p53, but not in cells transfected with the control vector. These data suggest that re-establishing p53 function in MCF-7 breast cancer cells renders them more sensitive to the growth inhibitory effect of progesterone.

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Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma

International Journal of Oncology ◽

10.3892/ijo.2013.1783 ◽

2013 ◽

Vol 42 (3) ◽

pp. 1052-1060 ◽

Cited By ~ 15

Author(s):

MUCHUN ZHANG ◽

JINHUI WANG ◽

CHANG LI ◽

NINGNING HU ◽

KAI WANG ◽

...

Keyword(s):

Prostate Carcinoma ◽

Inhibitory Effect ◽

Oncolytic Adenovirus ◽

Growth Inhibitory Effect ◽

Growth Inhibitory ◽

Potent Growth

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Abstract 343: Inhibitory effect of oncolytic adenovirus on transforming growth factor- β-induced epithelial-mesenchymal transition in human cancer cells

10.1158/1538-7445.am2012-343 ◽

2012 ◽

Author(s):

Yuuri Hashimoto ◽

Hiroshi Tazawa ◽

Yasuo Urata ◽

Shunsuke Kagawa ◽

Toshiyoshi Fujiwara

Keyword(s):

Growth Factor ◽

Cancer Cells ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Human Cancer ◽

Transforming Growth Factor Β ◽

Inhibitory Effect ◽

Oncolytic Adenovirus ◽

Mesenchymal Transition ◽

Human Cancer Cells

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Role of wild type p53 and double suicide genes in interventional therapy of liver cancer in rabbits

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000800002 ◽

2012 ◽

Vol 27 (8) ◽

pp. 522-528 ◽

Cited By ~ 10

Author(s):

Hong-xin Niu ◽

Tong Du ◽

Zhong-fa Xu ◽

Xi-kun Zhang ◽

Ruo-gu Wang

Keyword(s):

Gene Therapy ◽

Liver Cancer ◽

P53 Gene ◽

Interventional Therapy ◽

Inhibitory Effect ◽

Cancer Growth ◽

Tumor Growth Rate ◽

Significant Difference ◽

Group 5 ◽

Group 2

PURPOSE: To investigate the feasibility of interventional lipiodol embolism and multigene therapy in combination with focal chemotherapy in the treatment of VX2 liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm in diameter were randomly divided into five groups (n=9 per group). In Group 1, animals were treated with 0.9% sodium chloride. In Group 2, animals received lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy. In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy. Ultrasonography and CT were performed before and at ten days after interventional therapy. RESULTS: The VX2 model of liver cancer was successfully established in rabbits and interventional therapy smoothly performed. At ten days after interventional therapy, significant difference in the tumor volume was noted among five groups (p<0.05) and different treatments could inhibit the cancer growth. The inhibition of cancer growth was the most evident in the Group 5. Factorial analysis revealed gene therapy with p53 or TK/CD and lipiodol embolism independently exert significantly inhibitory effect on cancer growth. In addition, the suppression on tumor growth rate was the most obvious in the Group 5. CONCLUSIONS: Combination of gene therapy with lipiodol embolism can effectively inhibit the cancer growth and prolong the survival time. These findings demonstrate the effectiveness of multigene therapy in combination with lipiodol embolism in the treatment of liver cancer.

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