| Background and AimsLung cancer, with the highest incidence and mortality of all malignant carcinoma, was one of the malignant diseases which severely threatened the human health. It was estimated that, there were about 1.35 million new cases of lung cancer and 1.18 million patients dying from mis disease every year throughout the world. In spite of the rapid development of lung cancer treatment such as operation, chemotherapy, radiotherapy and the scheduled multi-modality treatment et al. the survival rate at 5 years was still very low. For example, this rate is 15% in the USA, average 10% in Europe, and is lower in developing nations including PRC, about 8.9% in these countries. Small cell lung cancer (SCLC) is a special category in bronchiogenic carcinoma. Its characteristics are quick progression, early invasion and metastasis. Because of these characristics of SCLC, the prognosis of patients with SCLC is very poor. SCLC is sensitive to chemotherapy which can't be continued because of side effect and (or) multi-drug resistance. Dr.Bunn, the president of ASCO proposed that multi- disciplinary-therapy was adapted to all cancers in 2003. At same time, FDA proclaimed that thermotherapy had become the fifth therapeutic tool following operation, chemotherapy, radiotherapy and biotherapy and played an important role, especially it had a broad prospective that hyperthermia combined with chemotherapy and (or) radiotherapy in 1985.It was worthy of being investigated the sensitivity of different tumors to various chemotherapeutic drugs, hypothennic temperatures and durations. Paclitaxel was an effective chemotherapy agent in tumor treatment However, the effectiveness of its combination with hyperthermia was unclear. In the study, NCI-H446 cell lines were introduced to explore the sensitivity of hyperthermia, so as to provide thermo-chemotherapy basis for clinical practice.Materials and methods1 NCI-H446 cell lines and Paclitaxel were adopted in this study.2 Different temperatures (37℃, 39℃, 40℃, 41℃, 42℃, 43℃and 44℃), different times (30min, 60min and 90min) of hyperthermia and different doses(0μg/L, 30μg/L, 60μg/L, 120μg/L, 240μg/L and 480μg/L) of Paclitaxel were grouped respectively. MMT assay was used to measure the inhibiting rates of thermotherapy, chemotherapy and thermo-chemotherapy on cell growth. Semi-quantitative RT-PCR was applied to determine the expression of MMP-2 mRNA and TNF-a mRNA after thermotherapy, chemotherapy and thermo-chemotherapy with different doses of Paclitaxel(60μg/L,120μg/L and 240μg/L).Results1 30μg/L～120μg/L Paclitaxel could enhance the inhibiting effect on cell growth with the increase of Paclitaxel concentrations(P<0.05) and at 120μg/L, the effect got the best.2 NCI-H446 cells were treated with different temperatures and the differences between control group and 41℃, 43℃, 44℃and 43℃hypothermic groups were statistically significant (P <0.05).3 The inhibiting effect reached climax at 90 min hypothermic duration in comparison with other hypothermic durations; the inhibiting effect of 30min was greater than that of 60min, which might be the result of protective mechanism of heating shock proteins.4 According to principle of factorial design and specialty, the optional combination of hypothermic temperature, duration and Paclitaxel concentration in this study was 43℃, 90min and 120μg/L.5 The differences of MMP-2 mRNA expression in NCI-H446 cells between control group and thermotherapy groups and thermo-chemotherapy groups were statistically significant(P<0.05); the differences of TNF-a expression in NCI-H446 cell between control group and thermotherapy groups, chemotherapy 120μg/L and 240μg/L) groups and thermo-chemotherapy groups were statistically significant(P <0.05) ; so thermotherapy and thermo-chemotherapy might inhibit cell proliferation through decreasing the expression of MMP-2 and increasing that of TNF-a mRNA.Conclusions1 The optional combination of hypothermic temperature, duration and Paclitaxel concentration in this study was 43℃90 min and 120μg/L.2 Hyperthermia can enhance the inhibiting effect of Paclitaxel on NCI-H446 cell, probably by decreasing the expression of MMP-2 and increasing the expression of TNF-a.
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