Objective To investigate the effect and mechanism of hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) on sarcoma.Methods The intracellular uptake of HMME on osteosarcoma cells (LM8) and myoblast cells (C2C12) using flow cytometry method.The bone and soft sarcoma cells viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The apoptosis of osteosarcoma cells were detected by flow cytometry method with Annexin VFITC/PI staining.The apoptosis of cells was further observed by Hoechst 33342 staining.The irreversible inhibitor of caspase (Z-VAD-FMK) and necrosis (Nec-1) was performed to detect the type of PDT-mediated cell death.The relative expression levels of caspase-1,3,6,9 and PARP were detected by Western blotting and immunohistochemistry (IHC).The efficacy of antitumor was evaluated by the size and the weight and Hematoxylin eosin (HE) staining was used to observe the histological changes of tumor.Results HMME can selectively accumulate in osteosarcoma cells while normal cells absorbed much less.HMME-PDT can markedly killed the sarcoma cells and the killing effect increased with HMME concentration and energy intensity.The apoptosis rates in HMME-PDT groups significantly increased both adherent and suspension cells.It was observed typical changes,by Hoechst 33342 stained.The results showed that apoptosis was the major form of cells death and might be closely with caspase-dependent apoptosis after HMME-PDT.The expression levels of caspase-1,3,6,9 and PARP were significantly up-regulated in the treatment groups.Comparing with the blank group,the tumor volume and the tumor weight were markedly decreased.The widespread necrotic areas were observed by HE staining in tumor.Conclusion HMME-PDT significantly inhibited the tumor growth in vivo,which are closely correlated with caspase-dependent pathway. Key words: Hematoporphyrin photoradiation; Hematoporphyrins; Osteosarcoma; Sarcoma