p21 overexpression sensitizes osteosarcoma U2OS cells to cisplatin via evoking caspase-3 and Bax/Bcl-2 cascade.

Osteosarcoma is the most common form of primary malignant bone tumor that mainly occurs in juvenile patients. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that p21 plays important roles in regulating tumor growth. To study the effects of p21 on the chemosensitivity of human osteosarcoma U2OS cells to cisplatin and its relevant mechanisms, we stably transfect the pC-21-SN3 vector containing P21 to U2O3 cells (U2O3-p21), which was identified by RT-PCR and Western blot. The results showed that no p21 was expressed in U2OS and U2OS-vec cells, but it was highly expressed in U2O3-p21 cells at mRNA and protein levels. The growth of U2OS cells was almost not influenced by p21 alone. However, U2O3-p21 cells underwent more obvious apoptotic morphological changes than U2OS and U2OS-vec cells after being treated with cisplatin (5 μg) for 72 h. Besides, increased expression of cleaved caspase-3 and Bax/Bcl-2 ratio was observed in cisplatin-treated U2O3-p21 cells. These data clearly indicated that exogenous p21 gene transfection could enhance the cisplatin-induced cytotoxicity against human osteosarcoma U2OS cells, at least in part, by activating caspase-3 cascade and increasing Bax/Bcl-2 ratio.