Abstract
Melanoma, one of the aggressive cancers, is known to be resistant to chemotherapy. Because of its aggressive nature, effectively inducing apoptosis is necessary to treat melanoma. Erythroid differentiation regulator 1 (Erdr1) is known to be a stress-related survival factor exhibiting anti-cancer effects in several cancers. However, little is known about the functions and underlying mechanisms of Erdr1 so far. To demonstrate the effect of Erdr1 in melanoma apoptosis, recombinant murine Erdr1 was injected into mice implanted with B16F10 melanoma cells. In vivo tumor growth was significantly inhibited in mice injected with Erdr1 compared to the control. In addition, the tumor from Erdr1-injected mice showed an increased level of apoptosis. Accordingly, apoptosis-regulating factors including anti-apoptotic marker Bcl-2 and pro-apoptotic marker Bax in the tumor tissues were examined. As expected, the decreased level of Bcl-2 and increased level of Bax were detected in tumors within the mice injected with Erdr1. Based on the in vivo study, the role of Erdr1 in tumor apoptosis was further tested by incubating it with cells of the murine melanoma cell line B16F10. Erdr1-induced apoptosis in B16F10 cells was observed. Additionally, Erdr1 downregulated STAT3 activity, inhibiting apoptosis via regulation of the Bcl-2 family. Overall, data demonstrate that Erdr1 induced murine melanoma apoptosis through the regulation of Bcl-2 and Bax. These findings suggest that Erdr1 is a novel regulator of apoptosis in melanoma.
Highlights
Melanoma is highly resistant to many conventional chemotherapeutic drugs due to aberrant regulation of the apoptosis signaling pathway [1]
Based on these previous studies, we investigated the role of Erythroid differentiation regulator 1 (Erdr1) in melanoma
We demonstrated that Erdr1 acts as an apoptosis-stimulating factor for acts as a critical inducer of apoptosis [13]
Summary
Melanoma is highly resistant to many conventional chemotherapeutic drugs due to aberrant regulation of the apoptosis signaling pathway [1]. EErrddrr IInndduucceess AAppooppttoossiiss vviiaa RReegguullaattiioonn ooff BBccll--22 aanndd BBaaxx iinn VViivvoo. To determine the underlying mechanism of Erdr1-mediated apoptosis in melanoma, Int. J. To determine the underlying mechanism of Erdr1-mediated apoptosis in melanoma, SSTTAATT33 aacctitvivitiytyfoflolollwowinigngErEdrrd rt1reatrtmeaetmntewntaswmaesasmuereadsuirnedB16inF1B01c6eFll1s0uscienlglsDuNsiAn-gbiDndNinAg-bEiLndISiAngs. We demonstrated that Erdr acts as an apoptosis-stimulating factor for melanoma via the downregulation of Bcl-2 and upregulation of Bax, leading to increased apoptosis in melanoma cells both in vitro and in vivo. To identify the signaling molecules involved in Erdr1-mediated apoptosis, STAT3 activity was examined. Treatment of melanoma cells with Erdr inhibited STAT3 activity. Inhibition of STAT3 represses the expression of Bcl-2 and sensitizes cells to chemotherapy-induced apoptosis [18]. ABT-737, a small molecule that targets anti-apoptotic Bcl-2 family proteins, has a synergistic effect in killing melanoma cells in combination with the proteasome inhibitor Bortezomib [20]. Erdr acts as a novel regulator of apoptosis in melanoma
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