Abstract
MicroRNA‑21 (miR‑21) is a potential therapeutic target for melanoma. Whether miR‑21 inhibitor affects the anti‑cancer activity of doxorubicin assisted by c(RGDyK)‑modified liposome (DLN) in melanoma and the underlying mechanisms are largely unknown. In this study, in vitro and animal models were used to explore the effect of DLN combined with miR‑21 inhibitor on melanoma cells. The data demonstrated that treatment with 5 µl DLN (final concentration of doxorubicin 5 mg/ml) for 72 h effectively inhibited melanoma cell growth (~75% inhibition). The experiments were then divided into five groups: Control group, vector group, DLN group, miR‑21 inhibitor group and miR‑21 inhibitor + DLN group. Compared with the control group, DLN (5 µl) or miR‑21 inhibitor significantly reduced migration and invasion of melanoma cells, promoted apoptosis and arrested cells at the G1 phase. Notably, the combined application of DLN with miR‑21 inhibitor further promoted the anti‑cancer effects (reducing migration and invasion of melanoma cells, promoting apoptosis and arresting cells at G1 phase) compared with individual application of DLN or miR‑21 inhibitor. Mechanically, DLN did not function by reducing miR‑21 expression, whereas DLN and miR‑21 inhibitor downregulated B‑cell lymphoma-2 (BCL‑2) expression, and facilitated BCL‑2‑associated X protein (Bax) and P53 expression in melanoma cells. DLN and miR‑21 inhibitor together displayed stronger effects on Bcl‑2, Bax and P53 expression that each alone. In vivo data further demonstrated that DLN inhibited tumor growth further than a similar dose of doxorubicin only. Furthermore, miR‑21 inhibitor and DLN exerted the optimal anti‑cancer effect compared with single application of DLN or miR‑21 inhibitor. Together, the findings demonstrated miR‑21 inhibitor facilitated the anti‑cancer activity of DLN in melanoma, and the mechanisms involved Bcl‑2, Bax and P53 expression.