Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells

Abstract

Pigmented villonodular synovitis (PVNS) is a rare sarcoma-like disorder characterized by synovial lesions proliferation and invasion to articular cartilage for which no effective treatments are available. Imatinib mesylate (IM) is known to exert antitumor activity in some tumors, but its effects on PVNS fibroblast-like synoviocytes (PVNS-FLS) and the specific mechanism involved remain to be established. In the present study, the in vitro effects of IM on cell proliferation and survival rates were investigated in PVNS-FLS. Apoptosis induction was assessed via acridine orange/ethidium bromide (AO)/(EB) and Annexin V/PI staining as well as western blotting. The invasion ability of PVNS-FLS was evaluated by Transwell invasion chambers. IM significantly inhibited survival and invasion ability of PVNS-FLS in a dose- and time-dependent manner. The drug-treated cell groups exhibited markedly higher apoptosis, which was blocked upon pretreatment with the specific caspase-9 inhibitor Z-LEHD-FMK. Expression of cleaved caspase-9 was significantly increased and the Bcl-2 family and caspase-3 were activated following treatment with IM. Our results collectively demonstrated that IM has a strong antiproliferative effect on PVNS-FLS in vitro, attributable to induction of mitochondrial-dependent apoptosis in association with activation of caspase-9/-3 and the Bcl-2/Bax family, and exhibits significant inhibition on the invasion ability of PVNS-FLS, suggesting that IM may be useful as a novel treatment of this disease.

Oleanolic Acid Decreases IL-1β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF-κB Axis in Osteoarthritis

“…According to the CCK-8 assay result and previous studies, 100 μ M of OLA was used for the in vitro experiment [ 14 ]. Recently, some studies have found that mitochondrial dysfunction was involved in synovitis [ 16 ]. SIRT3 is located in the mitochondria and regulates mitochondrial function.…”

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: a study protocol

“…TGCT progresses slowly [21]. However, it causes local destruction with invasion of the adjacent joint cartilage [22], and more severe symptoms such as joint pain, limited range of motion, swelling, erythema, and hemorrhagic effusion [23]. Excision by arthroscopic or open synovectomy is recommended, but complete removal is sometimes difficult to achieve due to the wide spread of the growth, resulting in high local recurrence [4, 5].…”

Tender Nodules of the Foot

“…Pigmented villonodular synovitis, also known as tenosynovial giant-cell tumor, is a rare synovial proliferative disease with an incidence of 1.8 cases per 1 million people (Chen et al, 2015). Due to its rare incidence, the disease remains a diagnostic challenge.…”