ABSTRACT
Background and purpose:Oxaliplatin (L-OHP) is one of the most commonly used chemotherapy drugs in colorectal cancer and L-OHP-resistance is very common in colorectal cancer therapy. This research was to discuss the reversal effect in L-OHP-resistant human colon cancer cell line LoVo/L-OHP by anemoside B4 (AB4) and tetrandrine (Tet) and to clarify their molecular mechanism. Methods:LoVo/L-OHP cells were treated for 48 h by AB4 and Tet at different concentrations to get non-toxic dose. Drug sensitivity was measured by MTT. After the treatment, the cell cycle and apoptosis of the cells were detected. Expression of P-gp mRNA, zDHHC9 mRNA and SMAD4 mRNA were detected by RT-PCR. Expression of P-gp, zDHHC9 and SMAD4 protein were detected by Western blot. Results:The IC50 of LoVo/L-OHP for L-OHP was (112.5±23.6) μg/mL, and the IC50 decreased to (62.8±21.4) μg/mL (P0.05). The cell apoptosis experiment showed that the apoptotic rate increased after the treatment with AB4 and Tet with non-toxic dose but with no statistical signiifcance (P>0.05). The RT-PCR experiment showed that the expressions of P-gp mRNA and zDHHC9 mRNA were increased and SMAD4 mRNA was decreased in LoVo/L-OHP cells compared with in LoVo cells (P<0.05), while it was found that P-gp mRNA in LoVo/L-OHP cells was decreased after the treatment with AB4 at non-toxic dose (P<0.05). Western blot experiment showed the protein of P-gp in LoVo/L-OHP cells was decreased after treatment with AB4 (P<0.05), which was accordant to the PCR result. The expression of zDHHC9 protein in LoVo/L-OHP cells was decreased in LoVo/L-OHP cells after treatment with Tet (P<0.05). Conclusion:AB4 and Tet have some reversal effect on resistant to L-OHP in LoVo/L-OHP cells. The molec-ular mechanism of the resistance reverse effect was related to down-regulation of P-gp for AB4 and down-regulation of zDHHC9 for Tet.
ABSTRACT
Objective To further elaborate the clinical characteristics,diagnosis,treatment and prognosis of primary cutaneous invasive epidermo-tropic CD8 positive cytotoxicity T-cell lymphoma.Methods The clinical characteristics,diagnosis and treatment of a patient with primary cutaneous invasive epidermotropic CD8 positive cytotoxicity T-cell lymphoma were summarized,and diagnosis and treatment of the disease from published literature were reviewed.Results After one year long,recurrence of exudative maculopapule on his body and limbs,a middle-aged male patient visited our hospital.Then,the patient was diagnosed as T2N0M0 Ⅰ phase of primary cutaneous invasive epidermo-tropic CD8 positive cytotoxicity T-cell lymphoma based on results of skin biopsy,immunohistochemistry,T-cell gene rearrangement and PET-CT.Through integrative medicine treatment (combination of bruceolic oil emulsion and chemotherapy with GDP regimen),the patient achieved complete remission (CR).The treatment and follow-up continues till now and his condition was stable.Conclusions Clinical occurrence of primary cutaneous invasive epidermo-tropic CD8 positive cytotoxicity T-cell lymphoma is rare and early diagnosis is difficult.It could be diagnosed with histopathology combined with T-cell gene rearrangement.In order to avoid misdiagnosis,great caution should be taken during disease history inquiry and physical examination,should be early lesion for delayed healing of recurrent lesions,biopsy should be conducted as soon as possible and immunohistochemistry should be performed simultaneously,which will provide a good basis for further treatment.