Effect of lanthanum chloride on tumor growth and apoptosis in human ovarian cancer cells and xenograft animal models

摘要

Ovarian cancer is the leading cause of mortality resulting from gynecologic cancer. A common anti-ovarian tumor drug is cisplatin; however, repeated use of cisplatin causes severe resistance and leads to poor long-term survival rate in ovarian cancer patients. Recently, it was reported that lanthanum chloride (LaCl3) may inhibit tumor growth and induce apoptosis in certain cancer cells. In the present study, the effect of LaCl3 on ovarian cancer was determined in vivo and in vitro. A cisplatin-sensitive human ovarian cancer cell line, COC1, was used in the current study. A xenograft animal model of ovarian cancer was established injecting COC1 or cisplatin-resistant COC1 cells (COC1/DDP) cells into mice. A TUNEL assay was used to determine the apoptosis of the COC1 or COC1/DDP cells and a immunohistochemical assay was conducted to measure the expression of B-cell lymphoma-2, Ki67, breast cancer 1 (BRCA)1, BRCA2 and excision repair cross-complementation group 1 in COC1 or COC1/DDP cells. It was observed that LaCl3 promoted apoptosis in COC1 and COC1/DDP cells. In addition, LaCl3 plus cisplatin led to further increase in the expression levels of tumor suppressor genes and decrease in the expression of oncogenes. Furthermore, application of LaCl3 and cisplatin inhibited tumor growth in vivo in a xenograft animal model. These results indicated the synergistic role of LaCl3 on cisplatin-induced inhibition of cancer cell proliferation and tumor growth, providing a potential and effective candidate for the treatment of ovarian tumors.