| Background and objective:Cervical cancer is the most common malignant tumor, in which the incidence is on the rise and the age of onset tends to be younger in recent years. More and more patients pay attention to improving the quality of life and remaining the reproductive function. So, chemotherapy play an more important role in therapeutic method.The epidermal growth factor receptor (EGFR) expressed excessively on many kinds of malignant tumor, such as cervical cancer. The EGFR is closely related with the malignant behavior and prognosis. Recently, the inhibitors of EGFR became the focus of targeted therapy. Cetuximab(C225) is a common inhibitors of EGFR, which has a satisfactory antitumor efficiency against head and neck squamous cell carcinoma also colorectal carcinoma. Few research were reported about cetuximab treating cervical cancer.As compared with cisplatin (DDP), Nedaplatin (NDP) is the second generation organic platinum analogue. NDP has the same curative effects with DDP, at the same time NDP has lower digestive tract and kidney toxicity. The most common side effects of nedaplatin were myelosuppression, some patients had to suspend therapy because of seriously platelet reduction. Many researchers tried to seeking Nedaplatin thiazolidinedione to reduce the toxicity, some researchers pay more and more attention on the EGFR inhibitors combining with chemotherapy drugs. Some studies had been shown that cetuximab could enhance the efficient of chemotherapy drugs, however there was few studies on the effects of cetuximab combining with nedaplatin.This article is trying to study the proliferation and apoptosis effects of combinative application of nedaplatin and cetuximab on cervical carcinoma hela cell lines, and analysis the cetuximab application value on cervical cancer. Subjects and Methods:Hela cells were interfered by C225groups, NDP groups and combinative groups of C225and NDP. The concentration of C225groups was10mg/L、20mg/L、40mg/L、60mg/L、80mg/L、160mg/L; The concentration of NDP groups was1mg/L、5mg/L、10mg/L、20mg/L、40mg/L、60mg/L; Each concentration respectively interfered hela cells24hours,48hours,72hours. The inhibitory effects of C225and NDP on the proliferation hela cell lines were evaluated by MTT assay. Cell apoptosis and cycle were detected by flow cytometry.SPSS17.0Statistical analysis software was used to make a reasonable statistical analysis of the experimental data, α=0.05was considered as the detection standard.Results:1The cell inhibition rates were measured by MTT when C225single-agent affecting hela cells. It was found that With the increase of drug concentration (10mg/L,20mg/L,40mg/L,60mg/L,80mg/L), the inhibitory rate increased slowly, P>0.05, no significant difference were found. the cell inhibition rates of concentration160mg/L compared to the above the five drug concentrations, P <0.05, there was statistically significant difference. Each drug concentration with treatment time (24h,48h,72h), the inhibitory rate increased slowly, P>0.05, no significant difference were found. The C225single drug to inhibit the proliferation of hela cells may have no obvious concentration-and time-dependent.2The cell inhibition rates were measured by MTT when NDP single-agent affecting hela cells. It was found that NDP significantly inhibited the growth of hela cell line, and the inhibition showed dose-and time-dependent. There were significant differences between all the inhibition effects of different concentrations and hours, significant differences were considered at P<0.05. 3It was found that the combining inhibition effects were significantly exceeding the separated C225or NDP, significant differences were considered at P<0.05. When the inhibition effects did not arrive50%, the combinative application of C225and NDP was synergism. When the inhibition effects did reach or exceed50%, the combinative application of C225and NDP was addition.4The cell apoptotic rates of combination significantly exceeded the separated C225or NDP, significant differences were considered at P<0.05.5The separated C225or NDP could inhibit the cells on G0-G1period of cell cycle. When combine C225and NDP, the G0-G1period of cell cycle inhibition effects significantly enhanced, the S period of cell cycle reduced significantly, significant differences were considered at P<0.05. T he G2-M period of cell cycle did not obviously change.Conclusion:1Separated C225could inhibit the proliferation of hela cells effectively.2Separated NDP could inhibit the proliferation of hela cells effectively, but need high concentration.3Compared with the effects of C225or NDP separately at high concentrations, combination of C225and NDP at low concentrations proved to be much more effitive in the inhibition of the proliferation and induction of the apoptosis of hela cell lines. |
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