Antitumor Activity of γδ T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model

Introduction: The gastrointestinal malignancy, gastric cancer (GC), has a high incidence worldwide. Cisplatin is a traditional chemotherapeutic drug that is generally applied to treat cancer; however, drug tolerance affects its efficacy. Sodium butyrate is an intestinal flora derivative that has general anti-cancer effects in vitro and in vivo via pro-apoptosis effects and can improve prognosis in combination with traditional chemotherapy drugs. The present study aimed to assess the effect of sodium butyrate combined with cisplatin on GC.Methods: A Cell Counting Kit-8 assay was used to assess the viability of GC cells in vitro. Hoechst 33,258 staining and Annexin V-Phycoerythrin/7-Aminoactinomycin D were used to qualitatively and quantitatively detect apoptosis in GC cells. Intracellular reactive oxygen species (ROS) measurement and a mitochondrial membrane potential (MMP) assay kit were used to qualitatively and quantitatively reflect the function of mitochondria in GC cells. Western blotting was used to verify the above experimental results. A nude mouse xenograft tumor model was used to evaluate the anti-tumor efficacity of sodium and cisplatin butyrate in vivo.Results: Cisplatin combined with sodium butyrate increased the apoptosis of GC cells. In the nude mouse xenograft tumor model, sodium butyrate in combination with cisplatin markedly inhibited the growth of the tumor more effectively than either single agent. The combination of sodium butyrate and cisplatin increased the intracellular ROS, decreased the MMP, and suppressed the invasion and migration abilities of GC cells. Western blotting verified that the combination of sodium butyrate and cisplatin remarkably enhanced the levels of mitochondrial apoptosis-related pathway proteins.Conclusion: Sodium butyrate, a histone acetylation inhibitor produced by intestinal flora fermentation, combined with cisplatin enhanced the apoptosis of GC cells through the mitochondrial apoptosis-related pathway, which might be considered as a therapeutic option for GC.

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Gene Therapy for Human Nasopharyngeal Carcinoma by Adenovirus–Mediated Transfer of Human p53, GM-CSF, and B7-1 Genes in a Mouse Xenograft Tumor Model

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2007.0447 ◽

2008 ◽

Vol 23 (5) ◽

pp. 591-602 ◽

Cited By ~ 7

Author(s):

Su-Ping Ren ◽

Lan Wang ◽

Hua Wang ◽

Bin Wu ◽

Ying Han ◽

...

Keyword(s):

Gene Therapy ◽

Nasopharyngeal Carcinoma ◽

Tumor Model ◽

Xenograft Tumor ◽

Mouse Xenograft ◽

Gm Csf ◽

Human Nasopharyngeal Carcinoma ◽

Xenograft Tumor Model

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Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/468537 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Hongbo Wang ◽

Pengfei Yu ◽

Jing Bai ◽

Jianqiao Zhang ◽

Liang Kong ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Apoptosis ◽

Therapeutic Strategy ◽

Target Genes ◽

Tumor Model ◽

Xenograft Tumor ◽

Xenograft Tumor Model ◽

Hoechst Staining ◽

Dose Dependent ◽

Mtt Assays

The use of doxorubicin (Dox) was severely constrained by dose-dependent side effects, which might be attenuated by combining a “sensitizer” to decrease its cumulative dosage. In this study, it was investigated whether ocotillol could enhance the antiproliferation activity of Dox. MTT assays and xenograft tumor model were firstly conducted to evaluate the effect of ocotillol on the antitumor activity of Dox. Flow cytometry and Hoechst staining assays were then performed to assess cell apoptosis. Western blot and real-time PCR were finally used to detect the expression of p53 and its target genes. Our results showed ocotillol to enhance Dox-induced cell death in p53 wild-type cancer cells. Compared with Dox alone, Dox with ocotillol (Dox-O) could induce much more cell apoptosis and activate p53 to a much greater degree, which in turn markedly increased expression of proapoptosis genes. The enhanced cytotoxic activity was partially blocked by pifithrin-α, which might be through attenuating the increased apoptosis. Furthermore, ocotillol significantly increased the antitumor activity of Dox in A549 xenograft tumor in nude mice. These findings indicated that ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent apoptosis and suggested that coadministration of ocotillol with Dox might be a potential therapeutic strategy.

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