Yuan Liang

The fourth department of Internal Medicine, Liaoning Cancer Hospital& Institute, Shenyang.

Objective: Thisstudy was to investigate the effects of nimotuzumab combined paclitaxel againsthuman highly metastatic ovarian carcinoma cell line HO-8910PM, and explore themolecular mechanism of the combination. Method: HO-8910PMcells were added in RPMI1640 supplemented with 10% fetal bovine serum an l%glucose, cultured in a humidified 5% CO2/95% air atmosphere at 37℃. 1.While cells proliferated in logarithm, the effect of nimotuzumab alone orpaclitaxel alone, or the combination on the proliferation of HO-8910PM cellswas evaluated by MTT assay, and Q value was calculated to assess the combinedeffect. 2. The carcinoma cell line were inoculated in 6-hole plates, thendivided into four groups, receiving no treatment, or nimotuzumab alone, orpaclitaxel alone, or the combination respectively for 24hs. Flow cytometry(FCM) analysis was applied to detect the apoptosis. 3. The carcinoma cellline were inoculated in 6-hole plates, then divided into four groups, receivingno treatment, or nimotuzumab alone, or paclitaxel alone, or the combonationrespectively for 24hs. Werstern-blotting was used to detect the expression ofMEK, p-MEK, Akt and p-Akt, respectively. Result: 1.Nimotuzumab used alone inhibited the proliferation of HO-8910PM cells. With theconcentration of nimotuzumab ranging from 12.5ug/ml-100ug/ml, the inhibitioneffect increased positively, which showed significantly statistical differencecompared with the control group (P<0.001). Paclitaxel alone alsoinhibited the proliferation of HO-8910PM cells. With the dose of Paclitaxelranging from 6.25ug/ml-50ug/ml, the inhibition effect increased positively, significantlydifferent from the control group. (P<0.001, except when theconcertration was 6.25ug/ml for 24h (P>0.05)).2.The combination of nimotuzumab and paclitaxel could obviously inhibit theproliferation of HO-8910PM cells (P<0.001), which showed synergisticeffect at 24h and 48h, and an additive effect at 72h. 3. The combinationof nimotuzumab and paclitaxel could induce more apoptosis when used for24h. 4.The combination of nimotuzumab and paclitaxel could deeply decreasethe expression of MEK、p-MEK、Aktand p-Akt in the EGFR signaling pathway proteins. Conclusion: 1.Nimotuzumab or paclitaxel alone could inhibit the proliferation of highlymetastatic ovarian carcinoma cell HO-8910PM, and exihibit a synergistic effectwhen combined for 24h and 48h, and an additive effect at 72h. 2.Nimotuzumab enhanced the effect of paclitaxel by blocking the EGFR transductionpathway, which may be related to the entility of DNA and the activity ofcytokines of cell cycle, decreasing the chemotherapy-resistance. When combinedwith chemotherapy more damage which can’t be repaired can be induced, leadingto more apoptosis and enhancement of chemotherapy.

Key Words: Nimotuzumab  EGFR Paclitaxel