Apatinib Reverses Paclitaxel-resistant Lung Cancer Cells (A549) Through Blocking the Function of ABCB1 Transporter

Zhang, Quncheng; Song, Yan-Kui; Cheng, Xing; Xu, Zhiwei; Olajuyin, Ayobami Matthew; Wang, Jia; Sun, Zhifu

doi:10.21873/anticanres.13739

Cited by 16 publications

(12 citation statements)

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“…Furthermore, apatinib has been shown to reverse the resistance to PTX by affecting cell membrane-bound ATP-binding cassette (ABC) transporters, which extrude different chemotherapeutic agents out of the cancer cells. Apatinib reverses ABCB1-and ABCG2-mediated multidrug resistance by inhibiting their transport function (20,21). Nevertheless, the exact mechanisms were not the focus of the present exploratory study, and additional studies will be necessary to examine this point.…”

Section: Discussionmentioning

confidence: 97%

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study

Fan¹,

Li²,

Liu³

et al. 2020

Ann Transl Med

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Background: Apatinib combined with chemotherapy might be effective and safe for the management of advanced gastric cancer, but the available data are limited. To investigate the efficacy and safety of apatinib in combination with paclitaxel (PTX) alone or POF (PTX, oxaliplatin, and 5-fluorouracil) in patients with taxane-resistant advanced gastric cancer.Methods: Patients with taxane-resistant advanced gastric cancer were enrolled in the single-center, openlabeled, single-arm, exploratory study (ClinicalTrials.gov #NCT02697838). Apatinib was administered at 850 mg po in combination with weekly PTX or the POF regimen. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), the time to tumor progression (TTP), and safety.Results: Twenty participants were recruited from 08/2016 to 01/2018. The duration of the study treatment was 2.07 (0.03-16.2) months. The median follow-up was 24.8 (0.3-26.0) months. The reasons for termination of treatment were disease progression (n=6), adverse events (AEs) (n=5), and patients' will (n=9). The ORR was 11.1% (95% CI: 1.4-34.7%) and the DCR was 77.8% (95% CI: 52.4-93.6%). The median PFS was 3.5 (95% CI: 1.9-5.1) months, the median OS was 4.7 (95% CI: 2.0-7.3) months, and the median TTP was 4.2 (95% CI: 0.562-7.838) months. All 20 (100%) patients had AEs, 17 (85%) had apatinib treatment-emergent AEs (TEAEs), and 18 (90%) had chemotherapy TEAEs. The main grade 3-4 TEAEs were neutropenia, leukopenia, hypertension, and anemia.Conclusions: This preliminary study suggests that apatinib combined with PTX or POF might be effective and tolerable in patients with chemotherapy-refractory gastric cancer. Studies are necessary to confirm the results.Trial registration: ClinicalTrials.gov #NCT02697838.

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Section: Discussionmentioning

confidence: 97%

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study

Fan¹,

Li²,

Liu³

et al. 2020

Ann Transl Med

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“…Bevacizumab has shown some efficacy in the treatment of metastatic breast cancer, and chemotherapy as a first-line and second-line treatment for HER2-negative metastatic breast cancer has significantly extended median progression-free survival (PFS) ( 5 , 6 ). Preclinical studies have shown that antiangiogenic drugs combined with chemotherapy can improve the efficacy of chemotherapeutic drugs and reverse the resistance of tumor cells ( 7 – 9 ), which indicates this combination therapy may be a potential treatment.…”

Section: Introductionmentioning

confidence: 99%

A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer

Zhu

et al. 2021

Front. Oncol.

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IntroductionWe performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).MethodsPatients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0–1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.ResultsThirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0–7.9], and 6.9 months (95% CI 5.3–8.6) and 6.6 months (95% CI 1.4–11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4–29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).ConclusionApatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT03535961.

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“…Among them, ABCB1 is highly expressed in patients with lung adenocarcinoma and associated with poor survival [ 19 ]. ABCB1 inhibitors can overcome resistance to CDDP [ 20 ], doxorubicin (DXR, an anthracycline antibiotic) [ 21 ], and paclitaxel (a taxane-derived chemotherapeutic agent) [ 22 ], in human lung adenocarcinoma cells. Recently, the formation of tumor microenvironment by extracellular matrix, cancer cells, and non-cancerous cells has been reported to be involved in the chemoresistance [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Chemoresistance by Mg2+ Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells

Onuma

Manabe

Yoshino

et al. 2021

Cells

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Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg2+ deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg2+ concentration (LM) on proliferation and chemosensitivity using human lung adenocarcinoma A549 cells. Cell proliferation was reduced by continuous culture with LM accompanied with the elevation of G1 phase proportion. The amounts of reactive oxygen species (ROS) and stress makers such as phosphorylated-ataxia telangiectasia mutated and phosphorylated-p53 were increased by LM. Cell injury was dose-dependently increased by anticancer drugs such as CDDP and doxorubicin (DXR), which were suppressed by LM. Similar results were obtained by roscovitine, a cell cycle inhibitor. These results suggest that LM induces chemoresistance mediated by ROS production and G1 arrest. The mRNA and protein levels of ATP binding cassette subfamily B member 1 (ABCB1) were increased by LM and roscovitine. The LM-induced elevation of ABCB1 and nuclear p38 expression was suppressed by SB203580, a p38 MAPK inhibitor. PSC833, an ABCB1 inhibitor, and SB203580 rescued the sensitivity to anticancer drugs. In addition, cancer stemness properties were suppressed by SB203580. We suggest that Mg2+ deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation.

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Apatinib Reverses Paclitaxel-resistant Lung Cancer Cells (A549) Through Blocking the Function of ABCB1 Transporter

Cited by 16 publications

References 0 publications

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study

A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer

Upregulation of Chemoresistance by Mg2+ Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells

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