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Objective To confirm whether taxotere combined with mild hyperthermia will have synergistic effects,and to explore their joint mechanism of action.Methods Firstly the effective concentration of taxotere was determined by using MTT method to observe the effect of docetaxel on proliferation of human breast cancer cell line MCF-7.Then three samples of in vitro cultured human breast carcinoma MCF-7 cells were prepared,termed the the taxotere group,the taxotere plus mild hyperthermia group and the control group,and treated with effective concentration of taxotere exclusively or in combination with mild hyperthermia,or left without any special treatment.The taxotere plus mild hyperthermia group was subdivided into 5 subgroups according to the temperatures used (39.0 ℃,39.5 ℃,40.0 ℃,40.5 ℃,41.0 ℃) MTT assays were used to measure the proliferation and invasive capacity of the cells and their effective concentrations.Flow cytometry was used to detect cell apoptosis rates and any cell cycle changes in the control group.Western blotting was used to detect any changes in the expression of mitogen-activated protein kinases (MAPKs),Bcl-2/Bax,heat shock protein-70 (HSP-70) and P-gp.Results The taxotere with mild hyperthermia group demonstrated a significantly higher rate of apoptosis than that in the taxotere and control groups.There were also more cells in the G2/M phase observed.Combining taxotere with mild hyperthermia was found after 24 h to have significantly increased p-ERK,p-JNK,p38,HSP-70 and P-gp protein levels and to have significantly decreased Bcl-2 protein expression in contrast with the other two groups.Conclusions Combining taxotere with mild hyperthermia showed synergistic effects in vitro.It seemed to be limiting the accumulation of MCF-7 cells in the G2/M phase and activating the signal pathways of MAPKs while inhibiting the activation of Bcl-2/Bax signal pathways.Combining taxotere and mild hyperthermia can accelerate the expression of HSP70 and P-gp in MCF-7 cells.Hyperthermia might induce chemotherapy resistance.
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Objective To investigate the effect of mild hyperthermia on chemoresistance of gemcitabine in the pancreatic cancer cell line PANC1.Methods The PANC1 cell was treated with gemcitabine ( 1 μmol/L) for 1 h,then was heated at 37℃,42℃ and 45℃ for 1 hour,and was cultured for 0 h,24 h,48 h.Cell growth was analyzed by CCK-8 assay.Cell apoptosis was analyzed by Annexin Vfluorescein isothiocyanate ( FITC)/propidium iodide (PI) staining.Results The proliferation of cells at 42℃ and 45℃ for 24 h and 48 h were significantly lower than that at 37℃ (0.96 ± 0.05,0.88 ± 0.03vs 1.05 ±0.02;1.28 ±0.04,0.94 ±0.04vs 1.49 ±0.09;t =4.367,25.120,P ＜0.05).The proliferation of cells at 45℃ was significantly lower than that at 42℃ (t =3.348,11.732,P ＜0.05).The cell apoptosis rates at 37℃,42℃,45℃ after 48 h were (7.125 ±0.064)％,(9.985 ±0.615)％,(14.845 ± 1.987)％,the difference among the 3 groups was statistically significant (t =10.320,9.832,4.575,P ＜0.05).Conclusions Mild hyperthermia can reduce chemoresistance of gencitabine in pancreatic cancer cell PANC1.
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Objective:To investigate the radiosensitization and the cell-cycle of mild hyperthermia(≤42℃)on human pulmonary adenocarcinoma cell line SPC-A-1 in vitro. Methods: The human pulmonary adenocarcinoma cell line SPC-A were treated with radiation and the combination of radiation with mild hyperthermia. Radiosensitivity was determined by clonogenic assay and quantified by calculating the thermal enhancement ratio (TER). Flow cytometry was used to observe the cell-cycle. Results: Do, Dq calculated from the dose-response curve for radiation combined with 41.5℃ were 1.390 Gy, 1.426 Gy, whereas 1.693 Gy, 2.453 Gy for radiation alone, respectively. TER was 1.218. The proportion of cells in S phase was found to be 14.81% in the radiation group. The values, after 48 hours and 72 hours, with 6Gy radiation combined immediate 41.5℃ one hour mild hyperthermia, were 5.89% and 9.08%, respectively, versus 18.8% and 31.91% with 6 Gy radiation alone. Conclusion:Radiosensitization of mild hyperthermia in SPC-A-1 cells associated with the hyper-radiosensitization of the cells in S phase.
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PURPOSE: The aims of this study were to evaluate the change of [18F]fluoromisonidazole ([18F]FMISO) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia (42oC) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. METHODS AND MATERIALS: [18F]FMISO was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at 42oC for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air. The biodistribution of these agents were obtained at 3 h after [18F]FMISO injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10-micrometer sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. RESULTS: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for [18F]FMISO (1.56+/-1.03 vs. 0.67+/-0.30; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of [18F]FMISO uptake was significantly decreased. CONCLUSION: Mild hyperthermia and nicotinamide significantly improved tumor hypoxia using [18F]FMISO and this uptake reflected tumor hypoxic status.