Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma

Wu, Yufeng; Si, Ruirui; Tang, Hong; He, Zhen; Zhu, Huilian; Wang, Lili; Fan, Yingchao; Xia, Shunren; He, Zelai; Wang, Qiming

doi:10.1016/j.bbrc.2015.01.035

Cited by 42 publications

(43 citation statements)

References 29 publications

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“… 32 , 33 Additionally, dyslipidemias in lung cancer had been proved to increase the activity of tumor cells and reduce their sensitivity to chemotherapy, while its effects on chemotherapy in breast cancer could not be ruled out yet. 34 Thus, it is essential to take certain interventional measures against dyslipidemias in the process of breast cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients</p>

Lü

Zhu

et al. 2020

CMAR

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Purpose Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported. Methods From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared. Results It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen. Conclusion In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.

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Section: Discussionmentioning

confidence: 99%

<p>Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients</p>

Lü

Zhu

et al. 2020

CMAR

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“… 12 , 13 , 14 Elevated cholesterol level has been found in various tumors, including prostate, lung, acute myeloid leukemia and breast cancer, 15 , 16 , 17 , 18 especially in chemoresistant tumors. 19 , 20 Cholesterol accumulation in solid tumors promotes the proliferation, differentiation and migration of tumor cells by mediating cellular surface molecules, such as caveolin-1 translocation. 21 Depletion of membrane cholesterol suppresses the phosphorylation of Akt and ERK.…”

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confidence: 99%

4-cholesten-3-one suppresses lung adenocarcinoma metastasis by regulating translocation of HMGB1, HIF1α and Caveolin-1

et al. 2016

Cell Death Dis

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Metastasis is a great challenge in lung adenocarcinoma (ADC) therapy. Cholesterol has been implicated in ADC metastasis. 4-cholesten-3-one, as cholesterol metabolite and analog, can substitute membrane cholesterol and increase membrane fluidity. In this study, we explored the possibility that 4-cholesten-3-one inhibited ADC metastasis. Low-dose 4-cholesten-3-one significantly restrained ADC cells migration and invasion with little effects on cells viabilities. Further investigation showed that 4-cholesten-3-one promoted ROS generation, which transiently activated AMPKα1, increased HIF1α expression, reduced Bcl-2 expression and caused autophagy. AMPKα1 knockdown partly suppressed 4-cholesten-3-one-induced autophagy but, neither prevented 4-cholesten-3-one-induced upregulation of HIF1α or downregulation of Bcl-2. 4-cholesten-3-one-induced autophagy facilitated the release of HMGB1 from nuclei to cytoplasm, blocking nuclear translocation of HIF1α and activation of MMP2 and MMP9. Also, 4-cholesten-3-one induced time-dependent phosphorylation of caveolin-1, Akt and NF-κB. With increasing treatment time, 4-cholesten-3-one accelerated caveolin-1 internalization, but reduced the phosphorylation of Akt and NF-κB, and inhibited the expression of snail and twist. These data suggested that 4-cholesten-3-one could be a potential candidate for anti-metastasis of lung adenocarcinoma.

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“…Prior studies of lung and ovarian cancers consistently reported that cholesterol levels may affect the efficacy of platinum-based chemotherapeutic agents. 50,51 Our findings indicate a new link between genetic variants in BRCA2 and platinum-based chemotherapy response through cholesterol level regulation.…”

Section: Discussionmentioning

confidence: 68%

Gene networks and expression quantitative trait loci associated with platinum-based chemotherapy response in high-grade serous ovarian cancer

Choi¹,

Tarnouskaya

Nesdoly

et al. 2019

Preprint

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Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma

Cited by 42 publications

References 29 publications

<p>Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients</p>

<p>Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients</p>

4-cholesten-3-one suppresses lung adenocarcinoma metastasis by regulating translocation of HMGB1, HIF1α and Caveolin-1

Gene networks and expression quantitative trait loci associated with platinum-based chemotherapy response in high-grade serous ovarian cancer

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