A new method to induce multi-drug resistance to carboplatin in a mouse model of human tongue squamous cell carcinoma

Feng, Ge; Wang, D.-Z.; Chen, H.-Q.; Hu, Jia; He, Jiang

doi:10.1016/j.ijom.2008.06.014

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…However, despite the introduction of high-precision radiotherapy techniques and new systemic chemotherapeutic agents, a significant percentage of patients develop resistance to RT, and inevitably progress without cure. In patients diagnosed with Stage III and IV disease, the average five-year survival rate is 50% or less (1,2). Clinically, the identification and treatment of radioresistant SCCHN remains an unsolved problem.…”

Section: Introductionmentioning

confidence: 99%

Honokiol Radiosensitizes Squamous Cell Carcinoma of the Head and Neck by Downregulation of Survivin

Wang

Beitler

Huang

et al. 2018

Clinical Cancer Research

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Purpose Previous studies revealed diverging results regarding the role of survivin in squamous cell carcinoma of the head and neck (SCCHN).This study aimed to evaluate the clinical significance of survivin expression in SCCHN; the function of survivin in DNA damage repair following ionizing radiationtherapy (RT) in SCCHN cells; and the potential of honokiol to enhance RT through downregulation of survivin. Experimental Design Expression of survivin in SCCHN patient primary tumor tissues (n=100) was analyzed and correlated with clinical parameters. SCCHN cell lines were used to evaluate the function of survivin and the effects of honokiol on survivin expression in vitro and in vivo. Results Overexpression of survivin was significantly associated with lymph nodes metastatic status (p=0.025), worse overall survival (OS) and disease free survival (DFS) in patients receiving RT (n=65, OS: p=0.024, DFS: p=0.006) and in all patients with SCCHN (n=100, OS: p=0.002, DFS: p=0.003). In SCCHN cells, depletion of survivin led to increased DNA damage and cell death following RT, whereas overexpression of survivin increased clonogenic survival. RT induced nuclear accumulation of survivin and its molecular interaction with γ-H2AX and DNA-PKCs. Survivin specifically bound to DNA DSB sites induced by I-SceI endonuclease. Honokiol (which downregulates survivin expression) in combination with RT significantly augmented cytotoxicity in SCCHN cells with acquired radioresistance and inhibited growth in SCCHN xenograft tumors. Conclusions Survivin is a negative prognostic factor and is involved in DNA damage repair induced by RT. Targeting survivin using honokiol in combination with RT may provide novel therapeutic opportunities.

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Section: Introductionmentioning

confidence: 99%

Honokiol Radiosensitizes Squamous Cell Carcinoma of the Head and Neck by Downregulation of Survivin

Wang

Beitler

Huang

et al. 2018

Clinical Cancer Research

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Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases

et al. 2010

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Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells

Chen¹,

Lin²,

Chuang

et al. 2010

Anti-Cancer Drugs

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Triptolide, a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, exerts an antitumor effect in KB cancer cells through the induction of apoptosis. In this study, we show that triptolide possesses an anticancer effect on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax cells that overexpress multidrug resistance protein and MDR, respectively. Our data revealed that triptolide decreases the expression of multidrug resistance protein and MDR in both KB-7D and KB-tax cells. It also induces apoptosis in these multidrug-resistant cancer cells by activating caspase-3, and decreasing Mcl-1 and XIAP. Triptolide not only inhibits tumor growth but also induces apoptosis of these drug-resistant cancer cells in xenograft mouse models. Moreover, we also show that triptolide combined with 5-fluorouracil could be an alternative strategy for chemotherapy enhancement. These results indicate the therapeutic value of triptolide on multidrug-resistant cells, and when combined with 5-fluorouracil for the enhancement of cancer therapy.

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A new method to induce multi-drug resistance to carboplatin in a mouse model of human tongue squamous cell carcinoma

Cited by 3 publications

References 21 publications

Honokiol Radiosensitizes Squamous Cell Carcinoma of the Head and Neck by Downregulation of Survivin

Honokiol Radiosensitizes Squamous Cell Carcinoma of the Head and Neck by Downregulation of Survivin

Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases

Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells

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