Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway.

Non-small cell lung cancer (NSCLC) is the dominant type of lung cancer. Molecular targeting has highly improved the treatment efficacy of lung cancer, but new challenges have emerged, such as gefitinib-resistance and cancer recurrence. Therefore, new chemotherapeutic agents and treatment strategies are urgently needed. Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao', which has been shown to exhibit powerful anti-cancer activity in certain types of cancer; however, its activity in gefitinib-resistant lung cancer has never been addressed. In this study, we used a high-throughput screening assay for epidermal growth factor receptor (EGFR) inhibitors and discovered that Shikonin is a potent inhibitor of EGFR. The cytotoxicity of Shikonin and its anti-cancer mechanism in NSCLC was deeply explored. Shikonin exhibited selective cytotoxicity among two NSCLC cell lines (H1975 and H1650) and one normal lung fibroblast cell line (CCD-19LU). Shikonin significantly increased the activity of caspases and poly (ADP-ribosyl) polymerase (PARP), which are indicators of apoptosis, and the intensity of ROS by greater than 10-fold. NAC, an inhibitor of ROS, completely blocked apoptosis, caspase and PARP activation induced by Shikonin. Shikonin remarkably suppressed the phosphorylation of EGFR and led to EGFR degradation. The enhancement of ROS generation in H1650 and H1975 gefitinib-resistant NSCLC cells leads to impairment of growth and induction of apoptosis, whereas modulation of EGFR degradation and its downstream signalling pathways by Shikonin contributes to its anti-tumour properties in H1975 gefitinib-resistant NSCLC cells (with T790M and L858R activating mutations). Shikonin-induced cell apoptosis is closely associated with ROS elevation in the cells. These findings indicate that Shikonin can be an effective small molecule treating gefitinib-resistant NSCLC.

Factors predicting seroma formation after mastectomy for Chinese breast cancer patients.

BACKGROUND: Seroma formation after mastectomy typically delays recovery and adds to morbidity. AIMS: This retrospective review was undertaken to identify factors which predict development of seroma after mastectomy for breast cancer patients. SETTING AND DESIGN: 119 consecutive patients intended for mastectomy for the treatment of primary breast cancer were included. Factors taken into consideration were epidemiological, peri-operative in nature and those related to wound drainage output. MATERIALS AND METHODS: Total mastectomy was performed and axillary sampling was taken. All patients were reviewed within two weeks after leaving hospital, unless seroma formation was detected before discharge. The diagnosis of seroma was made clinically when a collection was detected beneath the skin flaps. STATISTICAL ANALYSIS USED: Student's t test was used with continuous variables and the X2 test for categorical situations. Fisher's exact test was applied when small numbers were encountered. A two-tailed test of P< 0.05 was considered significant. Univariate analyses were performed. RESULTS: The incidence of seroma formation was eight per cent. Five factors were identified to be significantly related to seroma formation: i) age over 45 years; ii) hypertension; iii) total drainage output exceeding 500 ml in the first three postoperative days; iv) drainage for more than eight days. Immediate breast reconstruction prevents the formation of seroma. CONCLUSION: The presence of hypertension in a patient over 45 years should alert the surgeon to possible seroma formation, particularly when the post-operative drainage exceeded 500 ml in the first three days. Appropriate preventive measures should then be implemented.