Hyperthermia increases the therapeutic efficacy of survivinT34A in mouse tumor models

Li, Zhimian; Zhao, Yuwei; Zhao, Cheng-Jian; Zhang, Xiaoping; Chen, Lijuan; Wei, Yuquan; Yang, Han-Shuo

doi:10.4161/cbt.12.6.15983

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…Furthermore, we have shown a remarkably prominent inhibition of tumor volume and size between hyperthermic and control conditions which further supports the significance of hyperthermia's therapeutic potential. A large number of studies are also in agreement with our in vivo findings although their focus was primarily on determining the efficacy of various clinical therapeutic protocols in combination with hyperthermia (43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Section: Discussionsupporting

confidence: 80%

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

et al. 2019

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Background: Several studies have highlighted hyperthermia's ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. Materials and Methods: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia's therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. Results: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. Conclusion: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage. One of the most aggressive and deadliest malignancies of all solid tumors is malignant melanoma (MM). Its incidence rates have been continuously rising worldwide while the disease accounts for the majority of skin cancer-related deaths (1-4). MM occurs from the accumulation of genetic and metabolic abnormalities of melanocytes as well as other contributing factors like numerous atypical nevi (i.e. benign proliferations of melanocytes), genetic predisposition and solar ultraviolet (UV) (5-7). In particular, evidence from various studies have linked exposure to UV radiation with the increased occurrence of the disease, due to the mutagenic properties of UVR, thus making it the leading risk factor (8-10). The majority of MM cases present an active BRAF mutation, with V 600E being the most common one accounting for 90% of cases. The activation of other oncogene pathways including RAS, c-KIT, NRAS, PI3K and PTEN as well as inactivation of tumor suppressors such as CDKN2A have been also associated with the development of the disease (11, 12). However, although there has been significant progress on understanding MM's biology, the disease's pathogenesis has yet to be well characterized. Although there is remarkable progress in developing more targeted therapeutic approaches there is still a great need to design more effective treatment strategies due to the poor responsiveness of MM to current therapeutic means (13-15). On the other hand, colorectal or colon carcinoma (CRC) is a tumor type originating from epithelial cells residing in the colon or rectum of the gastrointestinal tract (16, 17). CRC is the third most common type of cancer diagnosed globally while it is the fourth leading cause of cancer-related 2307 This article is freely accessible online.

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Section: Discussionsupporting

confidence: 80%

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

et al. 2019

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“…Several reports have presented evidence suggesting that ROS are involved in the regulation of cell death through various stimuli [16,31]. When cells are exposed to apoptotic stimuli, ROS are generated, and they induce mitochondrial permeability transition pore opening, the release of proapoptotic proteins, and the activation of caspase 9 [32].…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

Hou

Lin

Hou³

et al. 2014

IJMS

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Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS.

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“…In our laboratory, Peng et al (35) utilized survivinT34A plasmid (25 µg/one) complexed with cationic liposome (DOTAP:chol) by intravenous administration to inhibit tumor growth in female BALB/c mice bearing subcutaneous 4T1 mammary carcinoma. In another study by Li et al (36) investigated the synergistic antitumor effect by combining liposome-encapsulated mouse survivinT34A (20 µg/one) and hyperthermia in mouse colon cancer models. In this study, the gene delivery system we utilized was the same as previously reported (35,36), which proved to efficiently increase the therapeutic efficacy of the survivinT34A plasmid.…”

Section: Discussionmentioning

confidence: 99%

“…In another study by Li et al (36) investigated the synergistic antitumor effect by combining liposome-encapsulated mouse survivinT34A (20 µg/one) and hyperthermia in mouse colon cancer models. In this study, the gene delivery system we utilized was the same as previously reported (35,36), which proved to efficiently increase the therapeutic efficacy of the survivinT34A plasmid. Our previous biodistribution studies have showed that cationic lipid-DNA complexes was accumulated mainly in tumor tissues (37).…”

Section: Discussionmentioning

confidence: 99%

SurvivinT34A increases the therapeutic efficacy of arsenic trioxide in mouse hepatocellular carcinoma models

et al. 2016

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Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions. Disruption of survivin by the plasmid encoding the phosphorylation-defective mouse survivin threonine 34→alanine mutant (Msurvivin T34A plasmid) has proved a promising strategy for suppressing a variety of murine cancer. In the present study, we attempted to test Msurvivin T34A and arsenic trioxide (ATO) on a cell line and mice bearing subcutaneous tumors, with regard to their effects and mechanisms. We observed that the co-treatment with surivinT34A and ATO significantly enhanced the antitumor activity by induction of apoptosis in Hepa1-6 tumor cells in vitro, compared with control groups. The synergistic apoptosis-inducing effect of combination of these two drugs resulted in elevation of reactive oxygen species (ROS) level which could be antagonized by the antioxidant N-acetyl-l-cysteine. The combination treatment induced ROS-dependent collapse of the mitochondrial membrane potential. Moreover, the tumor growth in vivo was also remarkably inhibited by combination of surivinT34A and ATO when compared with control groups. Our findings demonstrate that the combination of surivinT34A and ATO exerted synergistic antitumor effects, providing a new perspective for clinical treatment of HCC.

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Hyperthermia increases the therapeutic efficacy of survivinT34A in mouse tumor models

Cited by 5 publications

References 34 publications

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

SurvivinT34A increases the therapeutic efficacy of arsenic trioxide in mouse hepatocellular carcinoma models

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