Polydatin ameliorates low-density lipoprotein cholesterol and lipid metabolism by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in triple-negative breast cancer with hyperlipidemia.
To investigate polydatin's effects on low-density lipoprotein cholesterol (LDL-C) and lipid metabolism in mice with triple-negative breast cancer (TNBC) and hyperlipidemia, as well as the underlying mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9). In vivo, we designed two animal models, namely breast pad in situ inoculation of TNBC model and TNBC with lung metastatic were inoculated with the caudal vein model. Mice were administered a high-fat diet. Upon the completion of the experiment, plasma triglycerides (TG), total plasma cholesterol (TC), plasma LDL-C, and plasma high-density lipoprotein cholesterol (HDL-C) were measured. ELISA was employed to measure PCSK9 and the low-density lipoprotein receptor (LDLR). The morphological alterations were observed using Oil-red O staining. Immunohistochemical labeling was used to determine the expression of PCSK9 and LDLR in mouse breast cancer (BC) tissues. MTT, wound healing assay, and the transwell migration and invasion test were conducted to examine co-cultured adipocytes' effects on the growth, invasion, and migration of BC cells. In the 4T1-luc cell model injected in situ into the breast pad and 4T1-luc cell model injected into the tail vein, we observed that a high-fat diet promoted the proliferation and lung metastasis of BC cells, whereas polydatin suppressed the proliferation and lung metastasis of BC cells. Co-culture of BC cells with adipocytes enhanced the proliferation, invasion, and metastasis, while polydatin intervention inhibited the growth, invasion, and metastasis. After treatment with polydatin, serum lipid levels decreased, PCSK9 decreased, LDLR increased, and LDL-C decreased in mouse BC, liver, and lung tissues. After polydatin treatment, PCSK9 decreased, LDLR increased, and LDL-C decreased in an in vitro co-culture system of BC cells and adipocytes. After transfection of siRNA PCSK9 in the co-culture system, the LDLR increased more significantly, and the LDL-C decreased more significantly. After transfection of LV-PCSK9, PCSK9 decreased, LDLR increased, and LDL-C decreased. We concluded that polydatin inhibited breast tumor proliferation and distant lung metastasis in mice promoted by a high lipid environment. By suppressing PCSK9, polydatin alters the lipid profile of hyperlipidemic TNBC mice and prevents distant metastases. Our findings provide credence to the established practice of using polydatin in treating TNBC combined with hyperlipidemia.
Liu M
，Zhang Q
《American Journal of Cancer Research》
The potential role and status of IL-17 family cytokines in breast cancer.
Breast cancer (BC) is currently the most common malignant tumor of women in the world. At present, the development of BC is accelerating and showing a younger trend, which may be due to the known and/or unknown risk factors (RFs) for BC are increasing. It has been reported that inflammatory factors promote the occurrence and development of BC. No doubt chronic inflammation could trigger a series of molecular events, which will lead to the malignant transformation of differentiated cells, inhibition of anti-tumor immunity, and finally, lead to the occurrence and metastasis of tumors. With the deepening of research, it has been found that pro-inflammatory cytokine-interleukin-17 (IL-17) is closely related to BC. It not only plays an important role in promoting tumor proliferation, invasion and metastasis, but also has a significant correlation with poor prognosis. Recently, it was reported that IL-17 is closely related to programmed death ligand 1 (PD-L1) in BC. Therefore, starting with the role of IL-17 family cytokines in BC, this paper briefly discusses the potential role and status of IL-17 and seeks to contribute to the development of targeted drugs for BC-related treatments and to the identification of prediction factors for the early detection and prognosis prediction of BC for laying a solid theoretical foundation.
Song X
，Wei C
，Li X
《-》
Correlations between serum lipid and Ki-67 levels in different breast cancer molecular subcategories.
Breast cancer has the highest incidence rate among all cancer types worldwide, seriously threatening women's health. The present retrospective study explored differences in serum lipid contents in different breast cancer (BC) subcategories and their correlation with Ki-67 expression levels in patients with invasive BC with the aim of identifying novel diagnostic and prognostic indicators for personalized BC treatment. The study included 170 patients diagnosed with BC who were diagnosed with invasive BC by postoperative pathological examination. Data on patient age, body mass index and menopausal status were collected, in addition to estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and antigen Ki-67 expression levels and pathological tumor type. Preoperative circulating lipid levels, specifically the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and apolipoproteins A1 (ApoA1) and B (ApoB) were also obtained. Molecular subcategories of BC were grouped based on their immunohistochemistry. Differences in serum lipid levels between the groups were assessed, and correlations between serum lipid and Ki-67 expression levels were explored. While TC, LDL-C, HDL-C and ApoA1 levels differed significantly among molecular subcategories. TG and ApoB levels did not. Circulating TC and LDL-C levels were considerably higher in patients with triple-negative BC (TNBC) and HER2-positive [hormone receptor (HR)-negative] BC than in those with luminal A and B (HER2-negative) BC. Serum HDL-C levels were significantly diminished in the TNBC and HER2-positive (HR-negative) groups compared with the luminal A and B (HER2-negative) groups. ApoA1 levels were significantly reduced in cases of TNBC and HER2-positive (HR-negative) BC compared with luminal A and B BC. Ki-67 expression levels were positively correlated with circulating TC and LDL-C levels and inversely correlated with circulating HDL-C and ApoA1 levels but exhibited no correlation with serum ApoB and TG levels. The results indicate that elevated TC and LDL-C levels and diminished HDL-C and ApoA1 levels were high-risk factors in patients with TNBC and HER2-positive (HR-negative) BC, but not patients with luminal subcategories of BC. Abnormal serum lipid levels were correlated with Ki-67 expression levels, with elevated circulating TC and LDL-C levels and reduced circulating HDL-C and ApoA1 levels indicating a poor prognosis in patients with BC.
Sun XB
，Liu WW
，Wang B
，Yang ZP
，Tang HZ
，Lu S
，Wang YY
，Qu JX
，Rao BQ
... -
《-》
The association between serum lipid levels and histological type of breast cancer.
Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC.
220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients' demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance.
There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p < 0.05). Patients with PR-negative BC were more likely to have high LDL-c and high LP(a) levels than patients with PR-positive one (p < 0.05). Multivariate logistic regression analysis showed that serum HDL-c (odds ratio (OR): 0.27, 95% confidence interval (CI) 0.10-0.76), LDL-c (OR: 0.19, 95%CI 0.04-0.93) and LP(a) (OR: 0.23,95%CI 0.07-0.80) levels were negatively associated with ER-positive BC, and serum HDL-c and LDL-c levels were significantly negatively associated with PR-positive BC (OR: 0.32, 95%CI 0.12-0.82; OR: 0.14, 95%CI 0.03-0.77). In addition, ER and PR positive BC was negatively associated with serum HDL-c and LDL-c levels (OR = 0.39, 95% CI 0.17-0.91; OR = 0.22, 95% CI 0.06-0.85) after adjusting with confounders. Serum HDL-c level (OR = 0.13, 95% CI 0.02-0.87) was still independently associated with ER and PR positive BC in postmenopausal women. The area under the curves (AUCs) of HDL-c to identify ER-positive BC, PR-positive BC, and ER and PR positive BC were 0.65 (95%CI 0.58-0.73, P < 0.01), 0.62 (95%CI 0.54-0.69, P < 0.01) and 0.64 (95%CI 0.56-0.72, P < 0.01), respectively.
Serum HDL-c and LDL-c levels were related to ER or PR positive BC. Lipid levels may also have acceptable performance in identifying BC histological type.
Wang X
，Wang Y
，Wang M
，Chen X
，Cui W
，Chen X
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
