Hydroxycamptothecin prevents intraarticular scar adhesion by activating the PERK signal pathway

Prospective application of stem cells to prevent post‐operative skeletal fibrosis

“…Owing to the anti‐fibrotic effect of anti‐tumor drugs, positive results have been achieved in reducing post‐operative skeletal fibrosis. Previous studies have shown that topical application of anti‐tumor drugs, including mitomycin C (MMC), 10‐hydroxycamptothecine (HCPT), colchicine and 5‐fluorouracil (5‐Fu), could prevent post‐operative skeletal fibrosis in animal models by inhibiting the inflammatory response, suppressing fibroblast proliferation and reducing collagen deposition. However, more research is needed to determine the exact effect of 5‐Fu .…”

“…Interestingly, a previous study has shown that topical application of 0.5 mg/ml MMC could prevent epidural fibrosis after microendoscopic discectomy surgery in 37 patients . Further evidence showed that anti‐tumor drugs could reduce post‐operative skeletal fibrosis by regulating miR‐200b and RhoE expression, upregulating NOXA expression, decreasing vascular endothelial growth factor (VEGF) expression, blocking the transforming growth factor beta (TGF‐β) pathway and activating the endoplasmic reticulum (ER) stress signaling pathway …”

“…In addition to the above mentioned mechanisms, others include the p38/MAPK pathway, regulation of miR‐let7c and the ER stress pathway . In particular, ER stress has been proven to be linked to post‐operative skeletal fibrosis . Induction of fibroblast apoptosis is considered a mechanism of preventing post‐operative skeletal fibrosis.…”

Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro

“…We further confirmed that HCPT could decrease the expression of TGF-β1-driven fibrotic genes in fibroblast. Recently, studies have shown that HCPT could reduce the expression of collagen in the New Zealand rabbit joint adhesion model (18). Similarly, in a rat model of bleomycin A5-induced pulmonary fibrosis, HCPT significantly decreased the expression of fibrotic gene type I collagen (33).…”

“…Hydroxycamptothecin (HCPT), a kind of camptothecin, is a cell cycle-specific anti-cancer alkaloid with low side effects and is widely used in the treatment of various cancers including gastric cancer, lung cancer, bladder cancer and liver cancer (14)(15)(16)(17). Recent studies have shown that HCPT could inhibit intra-articular joint scar adhesion (18,19), epidural scar adhesion after laminectomy (20) and postoperative glaucoma adhesion (21) by inhibiting fibroblast proliferation or inducing fibroblast apoptosis. Although HCPT has been shown to attenuate various adhesions, it remains unknown whether HCPT can ameliorate tendon adhesion.…”