PARK2 inhibits osteosarcoma cell growth through the JAK2/STAT3/VEGF signaling pathway

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor mainly occurring in children and adolescents. In past decades, studies revealed that PARK2 was a vital tumor suppressor gene in many malignant solid tumors. However, the role of PARK2 in OS remains largely unclear. Therefore, we assessed PARK2 expression in OS tissue and adjacent non-tumor tissues by immunohistochemical (IHC) analysis, and evaluated PARK2 mRNA expression in OS cell lines by real-time PCR analysis. The HOS and U2OS cell lines were employed to establish a PARK2 overexpression model. Using this model, we investigated the potential role of PARK2 in OS and explored the underlying molecular mechanisms. Our study showed PARK2 was downregulated in OS tissue and cell lines, which was significantly associated with higher tumor stage (P < 0.05). Overexpression of PARK2 arrested the cell cycle, inhibited cell proliferation, migration, and invasion, induced cell apoptosis, and reduced tube formation in vitro. Moreover, overexpression of PARK2 significantly suppressed tumor growth and angiogenesis in vivo. Additionally, PARK2 negatively regulated OS development through the JAK2/STAT3/VEGF pathway. Our findings demonstrate that PARK2 is a tumor suppressor gene that may negatively affect OS growth and angiogenesis via partly inhibiting the JAK2/STAT3/VEGF signaling pathway.

Phase I dose‐escalation trial to repurpose propagermanium, an oral CCL2 inhibitor, in patients with breast cancer

“…It is well known that the IL‐6/STAT3/vascular endothelial growth factor A axis plays a crucial role in tumor angiogenesis . Interleukin‐6 is downstream from CCL2 .…”

“…PG given as 30 mg/day (n = 3), 60 mg/day (n = 3), and 90 mg/day (n = 6) It is well known that the IL-6/STAT3/vascular endothelial growth factor A axis plays a crucial role in tumor angiogenesis. 20,21 Interleukin-6 is downstream from CCL2. [20][21][22] In a mouse model of metastatic BC, IL-6 was downregulated by CCL2 neutralization by anti-CCL2 Ab, resulting in inhibition of metastasis.…”

“…20,21 Interleukin-6 is downstream from CCL2. [20][21][22] In a mouse model of metastatic BC, IL-6 was downregulated by CCL2 neutralization by anti-CCL2 Ab, resulting in inhibition of metastasis. 23 Consistent with these reports, serum IL-6 levels were downregulated in a PG dose-dependent manner, implying that PG might have the potential to inhibit metastasis in human BC.…”

MiR‐216b inhibits osteosarcoma cell proliferation, migration, and invasion by targeting Forkhead Box M1

“…4 However, the rates of 10-year survival and long-term free survival are still unsatisfactory, which are about 50% or less, and the efficacy of related therapy is poor. 1-3 OS is chiefly located in the metaphysis of long bones, especially near the knee.…”

“…[1][2][3] OS is chiefly located in the metaphysis of long bones, especially near the knee. 4 However, the rates of 10-year survival and long-term free survival are still unsatisfactory, which are about 50% or less, and the efficacy of related therapy is poor. 5 Thus, there is a requirement to gain molecular insights into OS and identify useful therapeutic strategies to reduce recurrences in OS.…”