[Arsenic trioxide induces differentiation of human nasopharyngeal carcinoma in BALB/C nude mice xenograft model].
OBJECTIVE
There is evidence that arsenic trioxide (AS2O3) induce differentiation of leukemia cells; however, little is known about its effect on solid tumors. The aim of this study was to investigate whether AS2O3 can induce cell differentiation and its association with growth inhibition in human nasopharyngeal carcinoma using BALB/C nude mice xenograft model.


METHODS
Poorly differentiated human nasopharyngeal squamous carcinoma cells from CSNE-1 cell strain were transplanted subcutaneously to BALB/C nude mice to produce tumors. AS2O3 at a dose of 5 mg.(kg.d)-1 was given intraperitoneally for 10 consecutive days, and then 3 times a week for the following 3 weeks. The xenograft tumor growth in mice was observed after drug administration. The morphological changes of the tumors were examined under light and electron microscopy. Proliferating cell nuclear antigen (PCNA) expression was determined by immunohistochemistry.


RESULTS
AS2O3 at dose of 5 mg.(kg.d)-1 significantly inhibited the tumor growth in vivo, with a inhibitory rate of 75.4%. Remarkable cell differentiation induced by AS2O3 was observed under light microscope and transmission electron microscope, which was characterized by keratinization of tumor cells, decreased nuclear/cytoplasm ratio, increased cytoplasmic organelles and rich tonofibrils in cytoplasm. Desmosomes and micro-processes were much more frequently observed in tumors treated with AS2O3. Significantly decreased PCNA expression was observed in AS2O3-treated tumor cells. The PCNA-positive cell index (PI) was 53.6 +/- 7.0% in AS2O3-treated mice, and 95.2 +/- 5.0% in control, respectively (P < 0.001).


CONCLUSIONS
The growth of human nasopharyngeal carcinoma xenograft in BALB/C nude mice can be significantly inhibited by AS2O3, which might be related to the cell differentiation induced by AS2O3.
Du
Cai-Wen
CW
Cancer Research Laboratory, Cancer Hospital, Shantou, Guangdong, 515031, P. R. China.
Li
De-Rui
DR
Lin
Ying-Cheng
YC
Wu
Ming-Yao
MY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D010087:Oxides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D018809:Proliferating Cell Nuclear Antigen; D000077237:Arsenic Trioxide