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We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concentration of ADR by inhibiting the function and expression of P-gp at mRNA and protein levels in A549T cells. Additionally, the reversal effect of AFT on P-gp mediated multidrug resistance (MDR) might be related to the inhibition of PI3K/Akt pathway. Cotreatment with AFT and ADR could enhance ADR-induced apoptosis and autophagy in A549T cells. Meanwhile, the co-treatment significantly induced cell apoptosis and autophagy accompanied by increased expression of cleaved caspase-3, PARP, LC3B-II, and beclin 1. Apoptosis inhibitors had no significant effect on cell activity, while autophagy inhibitors decreased cell viability, suggesting that autophagy may be a self protective mechanism of cell survival in the absence of chemotherapy drugs. Interestingly, when combined with AFT and ADR, inhibition of apoptosis and/or autophagy could enhance cell viability. These results indicated that in addition to inhibit P-gp, ADR-induced apoptosis, and autophagy promoted by AFT contributed to the antiproliferation effect of combined AFT and ADR on A549T cells. These findings provide evidence that AFT combined ADR may achieve a better therapeutic effect to lung cancer in clinic.

Reliable multicast distribution is essential for some applications such as Internet of Things (IoT) alarm information and important file distribution. Traditional IP reliable multicast usually relies on multicast source retransmission for recovery losses, causing huge recovery delay and redundancy. Moreover, feedback implosion tends to occur towards multicast source as the number of receivers grows. Information-Centric Networking (ICN) is an emerging network architecture that is efficient in content distribution by supporting multicast and in-network caching. Although ubiquitous in-network caching provides nearby retransmission, the design of cache strategy greatly affects the performance of loss recovery. Therefore, how to recover losses efficiently and quickly is an urgent problem to be solved in ICN reliable multicast. In this paper, we first propose an overview architecture of ICN-based reliable multicast and formulate a problem using recovery delay as the optimization target. Based on the architecture, we present a Congestion-Aware Probabilistic Cache (CAPC) strategy to reduce recovery delay by caching recently transmitted chunks during multicast transmission. Then, we propose NACK feedback aggregation and recovery isolation scheme to decrease recovery overhead. Finally, experimental results show that our proposal can achieve fully reliable multicast and outperforms other approaches in recovery delay, cache hit ratio, transmission completion time, and overhead.