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P-16 The protection effect of a novel synthetic bismuth compound (BiZn) on cisplatin treated neuroblastoma tumor xenograft model
by 陳輔卿, 2015-10-25 07:46, 人氣(745)
P-16
 

The protection effect of a novel synthetic bismuth compound (BiZn) on cisplatin treated neuroblastoma tumor xenograft model

 

CHAN SHING1, Sun HZ2, Hong YF2, Ngan Ellis SW3, Man Nancy K3, Tam Paul KH3, Chan Godfrey CF1.

Departments of Paediatrics1 and Adolescent Medicine1, Chemistry2, Surgery3, the University of Hong Kong

 

Introductions: Cisplatin is a commonly used drug in chemotherapy. However one of the major side effects is nephrotoxcity. We developed a new orally administrated compound BiZn which can potentially protect the normal cells from cisplatin induced cytotoxic effects. We tested our hypothesis by using an in vitro and in vivo model.

Materials & methods: The effects of BiZn on a cisplatin treated panel of neuroblastoma cell lines were analyzed by XTT assay. The orthotopic xenograft model was prepared by injecting the in-house luciferase transfected neuroblastoma stem cells (SKNLP) into the adrenal gland of SCID Beige mice. Mice were divided into four groups: untreated, BiZn-treated, cisplatin treated, and BiZn plus cisplatin treated. BiZn pretreatment was conducted 24 hours after and just before cisplatin administration. BiZn was then administered every two days. A luminescent IVIS imaging system, equipped with Living Imaging software (Xenogen, Alameda, CA) was used to monitor the growth and metastasis of tumors in real time. We also examined mice blood BUN and survival rate under the BiZn and cisplatin treatment.

Results: The protective effects of BiZn on cisplatin treated neuroblastoma cells could be shown by XTT assay. For the in vivo model, the BiZn did not have anti-cancer effect on its own and also did not affect the therapeutic effect of cisplatin, both in the local site and the metastatic site. On the other hand, BiZn significantly reduced the levels of blood urea nitrogen in cisplatin treated mice. using the lethal dosage of cisplatin, co-treatment with BiZn significantly increased the survival rate of the mice. The mechanism of such protective effect has been identified and will be discussed.

Conclusions: Co-treatment of BiZn with Cisplatin can potentially decrease the cisplatin induced cytotoxicity. Furthermore, BiZn did not affect its antitumor activity. Since the new bismuth compounds can be used clinically with good oral absorption, BiZn may be readily applicable as a drug to counter the adverse effects of cisplatin.