PSD-007介导的光动力疗法治疗小鼠骨肉瘤的实验研究

目的 观察光敏剂PSD-007对小鼠骨肉瘤细胞LM-8的体外及体内光动力效应.方法 PSD-007与LM-8细胞共同孵育后以激光照射,应用MTT法测定光密度(OD540)值,计算抑制率.40只C3H小鼠接种LM-8细胞,皮下瘤块直径7～8 mm时随机分为:(1)对照组,空白对照、生理盐水加光照、注射PSD-007不光照;(2)光动力治疗组,分别注射5mg/kg、10mg/kg PSD-007,6 h后以激光照射.1周后测量瘤体大小、重量,计算抑瘤率并行病理学检查.C3H小鼠30只建立肿瘤模型,肿瘤直径达10～12mm时,分别行肿瘤边缘切除无光动力治疗(对照组)、边缘切除后240 J/cm2光动力治疗及边缘切除后360 J/cm2光动力治疗.4周后比较肿瘤复发率.结果 体外只光照或只注射PSD-007对LM-8细胞均无杀伤作应.PSD-007浓度越高、激光照射强度越大,LM-8细胞OD540值越小.PSD-007浓度>4μg/ml,光照强度>6 J/cm2时,抑制率>50%.光镜下细胞形态呈坏死或凋亡样改变.体内实验显示光动力治疗组的肿瘤体积及瘤重均减小,肿瘤边缘切除高强度激光照射组的复发率较对照组低.结论 PSD-007对LM-8细胞有明确的光动力抑制效应,其作用大小取决于其浓度和激光照射强度.光动力疗法可以降低肿瘤边缘切除后的复发率.

Abstract：

Objective To evaluate the PSD-007-mediated photodynamic effect on mouse osteosarcoma cell line LM-8, both in vitro and in vivo. Methods LM-8 cells were incubated with different concentrations of PSD-007 for 4 hours and then followed different laser irradiations. After photodynamic therapy (PDT), cell viability was measured using MTT assay and the optical density in each experiment was measured at 450 nm with a micro plate reader. The inhibition rate of cell growth was calculated. Four-week-old female C3H mice were used for implantation of LM-8 cells. When the diameter of tumor reached up to 7-8 mm, the mice were randomly divided into following groups: 1) control group, including untreated control, saline with laser irradiation, PSD-007 without laser irradiation; 2) PDT group, PSD-007 (5 and 10 mg/kg) was injected intravenously into the mice, and the tumor site was irradiated with laser light 6 hours after injection. Seven days after PDT, the size and weight of the tumors were measured. The inhibition rate of tumor was calculated, and all tumor specimens were taken for pathologic examination. After the diameter of tumor was 10-12 mm, the tumors were performed a marginal resection and subsequently followed 3 different treatments: without PDT (control), PDT with 240 J/cm2 or 360 J/cm2 laser irradiation. After 4 weeks treatment, the tumor recurrence rates were analyzed. Results MTT assay revealed that the cytotoxic effect of PDT on the LM-8 cells was positively correlated with the concentration of PSD-007 and the level of laser irradiation. When the concentration exceeded 4μg/ml, and the energy exceeded 6 J/cm2, the inhibition ratio was over 50%. No anti-tumor effect was observed in the cells treated with only laser irradiation or PSD-007 injection. Compared with the control group, the size and weight of the tumors were obviously decreased after PDT. PDT performed after marginal resection of the tumor reduced the rate of local recurrence. Conclusion PDT with PSD-007 showed cytotoxic effect on the LM-8 cells, and which performed after marginal resection of the tumor reduced the rate of local recurrence.

The research on effect of photodynamic therapy with PSD-007 on mouse osteosarcoma

Objective To evaluate the PSD-007-mediated photodynamic effect on mouse osteosarcoma cell line LM-8, both in vitro and in vivo. Methods LM-8 cells were incubated with different concentrations of PSD-007 for 4 hours and then followed different laser irradiations. After photodynamic therapy (PDT), cell viability was measured using MTT assay and the optical density in each experiment was measured at 450 nm with a micro plate reader. The inhibition rate of cell growth was calculated. Four-week-old female C3H mice were used for implantation of LM-8 cells. When the diameter of tumor reached up to 7-8 mm, the mice were randomly divided into following groups: 1) control group, including untreated control, saline with laser irradiation, PSD-007 without laser irradiation; 2) PDT group, PSD-007 (5 and 10 mg/kg) was injected intravenously into the mice, and the tumor site was irradiated with laser light 6 hours after injection. Seven days after PDT, the size and weight of the tumors were measured. The inhibition rate of tumor was calculated, and all tumor specimens were taken for pathologic examination. After the diameter of tumor was 10-12 mm, the tumors were performed a marginal resection and subsequently followed 3 different treatments: without PDT (control), PDT with 240 J/cm2 or 360 J/cm2 laser irradiation. After 4 weeks treatment, the tumor recurrence rates were analyzed. Results MTT assay revealed that the cytotoxic effect of PDT on the LM-8 cells was positively correlated with the concentration of PSD-007 and the level of laser irradiation. When the concentration exceeded 4μg/ml, and the energy exceeded 6 J/cm2, the inhibition ratio was over 50%. No anti-tumor effect was observed in the cells treated with only laser irradiation or PSD-007 injection. Compared with the control group, the size and weight of the tumors were obviously decreased after PDT. PDT performed after marginal resection of the tumor reduced the rate of local recurrence. Conclusion PDT with PSD-007 showed cytotoxic effect on the LM-8 cells, and which performed after marginal resection of the tumor reduced the rate of local recurrence.