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1.
Journal of Zhejiang University. Science. B ; (12): 234-245, 2020.
Article in English | WPRIM | ID: wpr-1010530

ABSTRACT

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality globally. It accounts for the majority of primary liver cancer cases. Amyloid precursor protein (APP), a cell membrane protein, plays a vital role in the pathogenesis of Alzheimer's disease, and has been found to be implicated in tumor growth and metastasis. Therefore, to understand the relationship between APP and 5-fluorouracil (5-FU) resistance in liver cancer, Cell Counting Kit-8, apoptosis and cell cycle assays, western blotting, and reverse transcription-quantitative polymerase chain reaction (qPCR) analysis were performed. The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated, as compared with that in Bel7402 cells. Through successful construction of APP-silenced (siAPP) and overexpressed (OE) Bel7402 cell lines, data revealed that the Bel7402-APP751-OE cell line was insensitive, while the Bel7402-siAPP cell line was sensitive to 5-FU in comparison to the matched control group. Furthermore, APP overexpression decreased, while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells. Mechanistically, APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes (B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl)). Taken together, these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU, providing a new perspective for drug resistance.


Subject(s)
Humans , Amyloid beta-Protein Precursor/physiology , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Drug Resistance, Neoplasm , Fluorouracil/pharmacology , Liver Neoplasms/drug therapy , Mitochondria/physiology , Proto-Oncogene Proteins c-bcl-2/genetics , bcl-X Protein/genetics
2.
Chinese journal of integrative medicine ; (12): 106-111, 2012.
Article in English | WPRIM | ID: wpr-289698

ABSTRACT

<p><b>OBJECTIVE</b>To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS.</p><p><b>RESULTS</b>Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048).</p><p><b>CONCLUSION</b>Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Capsules , Carcinoma, Non-Small-Cell Lung , Drug Therapy , General Surgery , Case-Control Studies , Disease-Free Survival , Drugs, Chinese Herbal , Therapeutic Uses , Kaplan-Meier Estimate , Lung Neoplasms , Drug Therapy , General Surgery , Quality of Life
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