No abstract

Melanoma is a malignancy with high potential to invasion and treatment resistance. The α-melanocyte-stimulating hormone (α-MSH) signal transduction involving Wnt/β-catenin, c-Kit, and microphthalmia-associated transcription factor (MITF), a known pathway to produce melanin, has been demonstrated as one of cancer stem cell characteristics. This study was aimed to examine the effect of resveratrol, an abundant ingredient of grape and medicinal plants, on α-MSH signaling, viability, and invasiveness in melanoma cells. By α-MSH treatment, the melanin production in B16 melanoma cells was augmented as a validation for activation of α-MSH signaling. The upregulated expression of α-MSH signaling-related molecules β-catenin, c-Kit, and MITF was suppressed by resveratrol and/or STI571 treatment. Nuclear translocation of MITF, a hallmark of α-MSH signaling activation, was inhibited by combined treatment of resveratrol and STI571. At effective concentration, resveratrol and/or STI571 inhibited cell viability and α-MSH-activated matrix metalloproteinase- (MMP-)9 expression and invasion capacity of B16 melanoma cells. In conclusion, resveratrol enhances STI571 effect on suppressing the α-MSH signaling, viability, and invasiveness in melanoma cells. It implicates that resveratrol may have potential to modulate the cancer stem cell characteristics of melanoma.

A composite antitumor drug carrier platform, in which antitumor drug doxorubicin (DOX) loaded core-shell structured Cu9S5@mSiO2 nanoparticles were incorporated into poly(ε-caprolactone) and gelatin to form nanofibrous fabrics using an electrospinning process, was successfully assembled. The resultant multifunctional spun pieces could be implanted directly to the tumor site of mice using surgical procedures to achieve the orthotopic synergistic therapy combining the chemotherapy of the controlled release of DOX from mesoporous SiO2 with the photothermal treatment through the performance of the photothermal transformation of Cu9S5 under 980 nm laser irradiation in vivo. The experimental results in vivo demonstrated that the synergistic chemotherapy/photothermal treatment of DOX loaded Cu9S5@mSiO2 composite fibers under 980 nm laser irradiation has a more efficient tumor suppression effect, compared with a single chemotherapy of DOX loaded Cu9S5@mSiO2 composite fibers without the 980 nm laser irradiation or a single photothermal treatment from Cu9S5@mSiO2 composite fibers under 980 nm laser irradiation.